|
1
|
Saini C, Sapra L, Ramesh V, Puri P, Srivastava RK. Double positive IL-17A +IFN-γ +CCR6 + ILCs contribute towards the immunopathology of lepromatous leprosy. Immunol Lett 2025; 275:107012. [PMID: 40189156 DOI: 10.1016/j.imlet.2025.107012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 02/18/2025] [Accepted: 04/03/2025] [Indexed: 04/21/2025]
Abstract
Leprosy is a skin disease caused by Mycobacterium leprae, characterized by both localized and generalized immune responses. Th1/17 lymphocytes play a crucial role in the immune response against M. leprae. However, adaptive immunity alone is not sufficient to completely eradicate the pathogen, suggesting the involvement of other innate immune cells in pathogen removal. Therefore, we investigated innate lymphoid cells (ILCs), which are the innate counterparts of helper T cells in adaptive immunity and are known to produce IFN-γ and IL-17. In the present study, we evaluated the expression of ILC1 and ILC3 in borderline tuberculoid (BT) and lepromatous leprosy (LL) lesional skin by flow cytometry and real time PCR. Further, the expression of various in-situ genes, including cytokines, chemokines, cytokine receptors chemokine receptors, and transcription factors by qPCR in skin lesions of leprosy patients were analyzed. The phenotypes of ILC1 and ILC3 cells were determined as CD3negCCR6+CD19negIFN-γ+ and CD3negCCR6+CD19negIL-17A+, respectively, by flow-cytometry analysis. BT skin lesions represents high CCR6+expression on total ILCs as compared to LL patients. Our results clearly indicate that ILC1 and ILC3 were highly expressed in skin lesions of BT as compared to LL leprosy patients. Moreover, we observed that double positive (DP) CD3negCCR6+CD19negIFN-γ+IL-17A+ ILCs were up-regulated in LL and showed a pathogenic role. The gene expression of IL-17A and IFN-γ were found to be significantly positively correlated with the percentage of CCR6+ ILCs. On the other hand, CCR6neg ILCs were negatively correlated with ILC1 and ILC3 associated markers. Summarily our results clearly suggest that both ILC1 and ILC3 are important and immune-protective, on the contrary DP (IFN-γ+IL-17A+) ILCs may promote progression and immunopathology of leprosy.
Collapse
Affiliation(s)
- Chaman Saini
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India
| | - Leena Sapra
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India
| | - V Ramesh
- Department of Dermatology, ESI college and hospital, Faridabad, Safdarjung Hospital (SJH), New Delhi, India
| | - Poonam Puri
- Department of Dermatology, Safdarjung Hospital (SJH), New Delhi, India
| | - Rupesh K Srivastava
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
| |
Collapse
|
|
2
|
Wei ZX, Jiang SH, Qi XY, Cheng YM, Liu Q, Hou XY, He J. scRNA-seq of the intestine reveals the key role of mast cells in early gut dysfunction associated with acute pancreatitis. World J Gastroenterol 2025; 31:103094. [PMID: 40182603 PMCID: PMC11962851 DOI: 10.3748/wjg.v31.i12.103094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/09/2025] [Accepted: 02/21/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis (AP). Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood. AIM To explore the biological processes and mechanisms of intestinal injury associated with AP, and to find potential targets for early prevention or treatment of intestinal barrier injury. METHODS This study utilized single-cell RNA sequencing of the small intestine, alongside in vitro and in vivo experiments, to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms. RESULTS Seventeen major cell types and 33232 cells were identified across all samples, including normal, AP1 (4x caerulein injections, animals sacrificed 2 h after the last injection), and AP2 (8x caerulein injections, animals sacrificed 4 h after the last injection). An average of 980 genes per cell was found in the normal intestine, compared to 927 in the AP1 intestine and 1382 in the AP2 intestine. B cells, dendritic cells, mast cells (MCs), and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine. Enterocytes, brush cells, enteroendocrine cells, and goblet cells maintained numbers similar to the normal intestine, while cytotoxic T cells and natural killer (NK) cells increased. Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities. Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities. Activated MCs, secreted chemokine (C-C motif) ligand 5 (CCL5), promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction. CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury, suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
Collapse
Affiliation(s)
- Zu-Xing Wei
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Shi-He Jiang
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Xiao-Yan Qi
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yi-Miao Cheng
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Qiong Liu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Xu-Yang Hou
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Jun He
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| |
Collapse
|
|
3
|
Tao H, Geng J, Bai L, Su D, Zhao Y, Xu G, Zhang M. Regulation of innate lymphoid cell by microbial metabolites. J Mol Med (Berl) 2025:10.1007/s00109-025-02530-3. [PMID: 40128460 DOI: 10.1007/s00109-025-02530-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 03/26/2025]
Abstract
Innate lymphoid cells (ILCs) are a unique category of immune cell that lack antigen-specific receptors yet possess the capacity to detect signals from the surrounding tissue. The majority of ILCs reside in the lymphoid and mucosal tissues, maintaining close associations with the microbiota. Beyond the contributions of accessory cells and adaptive immune cells, accumulating studies demonstrate that microbial metabolites serve a crucial role in mediating the relationship between ILCs and the microbiota. In this review, we highlight and summarize the roles of microbial metabolites from different sources in modulating ILC subsets, proposing these metabolites as potential therapeutic mechanisms in ILC-mediated diseases.
Collapse
Affiliation(s)
- Hongji Tao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Jingjing Geng
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001, China
| | - Long Bai
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Dan Su
- Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA
| | - Yu Zhao
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA
| | - Guifang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
| | - Mingming Zhang
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001, China.
| |
Collapse
|
|
4
|
Wang X, Hong Y, Zou J, Zhu B, Jiang C, Lu L, Tian J, Yang J, Rui K. The role of BATF in immune cell differentiation and autoimmune diseases. Biomark Res 2025; 13:22. [PMID: 39876010 PMCID: PMC11776340 DOI: 10.1186/s40364-025-00733-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 01/17/2025] [Indexed: 01/30/2025] Open
Abstract
As a member of the Activator Protein-1 (AP-1) transcription factor family, the Basic Leucine Zipper Transcription Factor (BATF) mediates multiple biological functions of immune cells through its involvement in protein interactions and binding to DNA. Recent studies have demonstrated that BATF not only plays pivotal roles in innate and adaptive immune responses but also acts as a crucial factor in the differentiation and function of various immune cells. Lines of evidence indicate that BATF is associated with the onset and progression of allergic diseases, graft-versus-host disease, tumors, and autoimmune diseases. This review summarizes the roles of BATF in the development and function of innate and adaptive immune cells, as well as its immunoregulatory effects in the development of autoimmune diseases, which may enhance the current understanding of the pathogenesis of autoimmune diseases and facilitate the development of new therapeutic strategies.
Collapse
Affiliation(s)
- Xiaomeng Wang
- Department of Laboratory Medicine, Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yue Hong
- Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Jinmei Zou
- Department of Rheumatology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, China
| | - Bo Zhu
- Department of Laboratory Medicine, Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Chao Jiang
- Department of Orthopaedics, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Liwei Lu
- Department of Pathology, Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China
| | - Jie Tian
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
| | - Jing Yang
- Department of Rheumatology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, China.
| | - Ke Rui
- Department of Laboratory Medicine, Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
| |
Collapse
|
|
5
|
Mathias K, Machado RS, Cardoso T, Tiscoski ADB, Kursancew ACDS, Prophiro JS, Generoso J, Petronilho F. Innate lymphoid cells in the brain: Focus on ischemic stroke. Microvasc Res 2025; 157:104755. [PMID: 39427988 DOI: 10.1016/j.mvr.2024.104755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 10/10/2024] [Accepted: 10/15/2024] [Indexed: 10/22/2024]
Abstract
The innate immune system consists of a diverse set of immune cells, including innate lymphoid cells (ILCs), which are grouped into subsets based on their transcription factors and cytokine profiles. Among these are natural killer (NK) cells, group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Unlike T and B cells, ILCs do not express the diverse antigen receptors typically found on those cells. Although ILCs function in various systems, further research is needed to understand their role in the brain and their involvement in neurological diseases such as stroke. This review explores the general immunological aspects of ILCs, with a particular focus on their role in the central nervous system and the pathophysiology of ischemic stroke.
Collapse
Affiliation(s)
- Khiany Mathias
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil; Program in Health Sciences, Health Sciences Unit, University of South Santa Catarina, Tubarao, SC, Brazil
| | - Richard Simon Machado
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil; Program in Health Sciences, Health Sciences Unit, University of South Santa Catarina, Tubarao, SC, Brazil
| | - Taise Cardoso
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Anita Dal Bó Tiscoski
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Amanda Christine da Silva Kursancew
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Josiane Somariva Prophiro
- Program in Health Sciences, Health Sciences Unit, University of South Santa Catarina, Tubarao, SC, Brazil
| | - Jaqueline Generoso
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Fabricia Petronilho
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil.
| |
Collapse
|
|
6
|
Li Y, Jia Z, Liu X, Zhao H, Cui G, Luo J, Kong X. Single-cell sequencing technology to characterize stem T-cell subpopulations in acute T-lymphoblastic leukemia and the role of stem T-cells in the disease process. Aging (Albany NY) 2024; 16:13117-13131. [PMID: 39422621 PMCID: PMC11552640 DOI: 10.18632/aging.206123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 07/17/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Precursor T-cell acute lymphoblastic leukemia (Pre-T ALL) is a malignant neoplastic disease in which T-cells proliferate in the bone marrow. Single-cell sequencing technology could identify characteristic cell types, facilitating the study of the therapeutic mechanisms in Pre-T ALL. METHODS The single-cell sequencing data (scRNA-seq) of Pre-T ALL were obtained from public databases. Key immune cell subpopulations involved in the progression of Pre-T ALL were identified by clustering and annotating the cellular data using AUCell. Next, pseudo-temporal analysis was performed to identify the differentiation trajectories of immune cell subpopulations using Monocle. Copy number mutation landscape of cell subpopulations was characterized by inferCNV. Finally, cellphoneDB was used to analyze intercellular communication relationships. RESULTS A total of 10 cellular subpopulations were classified, with Pre-T ALL showing a higher proportion of NK/T cells. NK/T cells were further clustered into two subpopulations. Stem T cells showed a high expression of marker genes related to hematopoietic stem cells, Naive T cells had a high expression of CCR7, CCR7, RCAN3, and NK cells high-expressed KLRD1, TRDC. The cell proliferation was reduced and the activation of T cell was increased during the differentiation of stem T cells to Naive T cells. We observed interaction between stem T cells with dendritic cells such as CD74-COPA, CD74-MIF as well as co-inhibition-related interactions such as LGALS9-HAVCR2, TGFB1-TGFBR3. CONCLUSION Stem T cells were involved in the development of Pre-T-ALL through the regulatory effects of transcription factors (TFs) KLF2 and FOS and multiple ligand-receptor pairs.
Collapse
Affiliation(s)
- Yan Li
- Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
| | - Zhenwei Jia
- Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
| | - Xiaoyan Liu
- Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
| | - Hongbo Zhao
- Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
| | - Guirong Cui
- Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
| | - Jianmin Luo
- Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Xiaoyang Kong
- Department of Hematology, Handan First Hospital, Handan, Hebei 056001, China
| |
Collapse
|
|
7
|
Schindler V, Venhoff N. [Eosinophilic granulomatosis with polyangiitis: a review article]. Laryngorhinootologie 2024; 103:705-714. [PMID: 38964344 DOI: 10.1055/a-2214-1669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a poorer prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.
Collapse
Affiliation(s)
- Viktoria Schindler
- Klinik für Rheumatologie und Klinische Immunologie, Department Innere Medizin, Universitätsklinikum Freiburg, Freiburg, Germany
| | - Nils Venhoff
- Klinik für Rheumatologie und Klinische Immunologie, Department Innere Medizin, Universitätsklinikum Freiburg, Freiburg, Germany
| |
Collapse
|
|
8
|
Hoffmann MH, Kirchner H, Krönke G, Riemekasten G, Bonelli M. Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases. Ann Rheum Dis 2024; 83:1233-1253. [PMID: 38702177 DOI: 10.1136/ard-2023-224092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 04/22/2024] [Indexed: 05/06/2024]
Abstract
Due to optimised treatment strategies and the availability of new therapies during the last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art treatment cannot induce remission. Moreover, the risk for flares strongly increases once anti-inflammatory therapy is tapered or withdrawn, suggesting that underlying pathological processes remain active even in the absence of overt inflammation. It has become evident that tissues have the ability to remember past encounters with pathogens, wounds and other irritants, and to react more strongly and/or persistently to the next occurrence. This priming of the tissue bears a paramount role in defence from microbes, but on the other hand drives inflammatory pathologies (the Dr Jekyll and Mr Hyde aspect of tissue adaptation). Emerging evidence suggests that long-lived tissue-resident cells, such as fibroblasts, macrophages, long-lived plasma cells and tissue-resident memory T cells, determine inflammatory tissue priming in an interplay with infiltrating immune cells of lymphoid and myeloid origin, and with systemically acting factors such as cytokines, extracellular vesicles and antibodies. Here, we review the current state of science on inflammatory tissue priming, focusing on tissue-resident and tissue-occupying cells in arthritis and SSc, and reflect on the most promising treatment options targeting the maladapted tissue response during these diseases.
Collapse
Affiliation(s)
| | - Henriette Kirchner
- Institute for Human Genetics, Epigenetics and Metabolism Lab, University of Lübeck, Lübeck, Germany
| | - Gerhard Krönke
- Department of Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Gabriela Riemekasten
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
| | - Michael Bonelli
- Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
| |
Collapse
|
|
9
|
Lee JH, Sergi C, Kast RE, Kanwar BA, Bourbeau J, Oh S, Sohn MG, Lee CJ, Coleman MD. Aggravating mechanisms from COVID-19. Virol J 2024; 21:228. [PMID: 39334442 PMCID: PMC11430051 DOI: 10.1186/s12985-024-02506-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases. The pathophysiology of COVID-19 uses the following three mechanisms: (1) inflammasome activation mechanism; (2) cGAS-STING signaling mechanism; and (3) SAMHD1 tetramerization mechanism, which leads to IFN-I production. Interactions between the host and virus govern induction, resulting in multiorgan impacts. The NLRP3 with cGAS-STING constitutes the primary immune response. The expression of SARS-CoV-2 ORF3a, NSP6, NSP7, and NSP8 blocks innate immune activation and facilitates virus replication by targeting the RIG-I/MDA5, TRIF, and cGAS-STING signaling. SAMHD1 has a target motif for CDK1 to protect virion assembly, threonine 592 to modulate a catalytically active tetramer, and antiviral IFN responses to block retroviral infection. Plastic and allosteric nucleic acid binding of SAMHD1 modulates the antiretroviral activity of SAMHD1. Therefore, inflammasome activation, cGAS-STING signaling, and SAMHD1 tetramerization explain acute kidney injury, hepatic, cardiac, neurological, and gastrointestinal injury of COVID-19. It might be necessary to effectively block the pathological courses of diverse diseases.
Collapse
Affiliation(s)
- Jong Hoon Lee
- Science and Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
- Department of Geriatrics, Gyeonggi Medical Center Pocheon Hospital, 1648 Pocheon-ro Sin-eup-dong, Pocheon-si, Gyeonggi-do, 11142, Republic of Korea.
| | - Consolato Sergi
- Division of Anatomical Pathology, Children's Hospital of Eastern Ontario (CHEO), University of Ottawa, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada
| | - Richard E Kast
- IIAIGC Study Center, 11 Arlington Ct, Burlington, 05408 VT, USA
| | - Badar A Kanwar
- Haider Associates, 1999 Forest Ridge Dr, Bedford, TX, 76021, USA
| | - Jean Bourbeau
- Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre, Montréal, QC, Canada
| | - Sangsuk Oh
- Department of Food Engineering, Food Safety Laboratory, Memory Unit, Ewha Womans University, Seoul, 03670, Korea
| | - Mun-Gi Sohn
- Department of Food Science, KyungHee University College of Life Science, Seoul, 17104, Republic of Korea
| | - Chul Joong Lee
- Department of Anesthesiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Michael D Coleman
- College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, UK.
| |
Collapse
|
|
10
|
Wen Z, Qiu L, Ye Z, Tan X, Xu X, Lu M, Kuang G. The role of Th/Treg immune cells in osteoarthritis. Front Immunol 2024; 15:1393418. [PMID: 39364408 PMCID: PMC11446774 DOI: 10.3389/fimmu.2024.1393418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 09/02/2024] [Indexed: 10/05/2024] Open
Abstract
Osteoarthritis (OA) is a prevalent clinical condition affecting the entire joint, characterized by its multifactorial etiology and complex pathophysiology. The onset of OA is linked to inflammatory mediators produced by the synovium, cartilage, and subchondral bone, all of which are closely tied to cartilage degradation. Consequently, OA may also be viewed as a systemic inflammatory disorder. Emerging studies have underscored the significance of T cells in the development of OA. Notably, imbalances in Th1/Th2 and Th17/Treg immune cells may play a crucial role in the pathogenesis of OA. This review aims to compile recent advancements in understanding the role of T cells and their Th/Treg subsets in OA, examines the immune alterations and contributions of Th/Treg cells to OA progression, and proposes novel directions for future research, including potential therapeutic strategies for OA.
Collapse
Affiliation(s)
- Zhi Wen
- Department of Joint Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- Graduate School of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Liguo Qiu
- Graduate School of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Zifeng Ye
- Graduate School of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Xuyi Tan
- Department of Joint Orthopedics, The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Xiaotong Xu
- Department of Joint Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Min Lu
- Department of Joint Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Gaoyan Kuang
- Department of Joint Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| |
Collapse
|
|
11
|
Dao LTM, Vu TT, Nguyen QT, Hoang VT, Nguyen TL. Current cell therapies for systemic lupus erythematosus. Stem Cells Transl Med 2024; 13:859-872. [PMID: 38920310 PMCID: PMC11386214 DOI: 10.1093/stcltm/szae044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 05/11/2024] [Indexed: 06/27/2024] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged by the immune system. Although standard treatment options such as hydroxychloroquine (HCQ), glucocorticoids (GCs), and other immunosuppressive or immune-modulating agents can help to manage symptoms, they do not offer a cure. Hence, there is an urgent need for the development of novel drugs and therapies. In recent decades, cell therapies have been used for the treatment of SLE with encouraging results. Hematopoietic stem cell transplantation, mesenchymal stem cells, regulatory T (Treg) cell, natural killer cells, and chimeric antigen receptor T (CAR T) cells are advanced cell therapies which have been developed and evaluated in clinical trials in humans. In clinical application, each of these approaches has shown advantages and disadvantages. In addition, further studies are necessary to conclusively establish the safety and efficacy of these therapies. This review provides a summary of recent clinical trials investigating cell therapies for SLE treatment, along with a discussion on the potential of other cell-based therapies. The factors influencing the selection of common cell therapies for individual patients are also highlighted.
Collapse
Affiliation(s)
- Lan T M Dao
- Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi 100000, Vietnam
| | - Thu Thuy Vu
- Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi 100000, Vietnam
| | - Quyen Thi Nguyen
- Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi 100000, Vietnam
| | - Van T Hoang
- Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi 100000, Vietnam
| | - Thanh Liem Nguyen
- Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi 100000, Vietnam
- Vinmec International Hospital, Center of Regenerative Medicine and Cell Therapy, Vinmec Healthcare System, Hanoi 100000, Vietnam
- Vin University, College of Health Sciences, Hanoi 100000, Vietnam
| |
Collapse
|
|
12
|
Liu H, Guan L, Su X, Zhao L, Shu Q, Zhang J. A broken network of susceptibility genes in the monocytes of Crohn's disease patients. Life Sci Alliance 2024; 7:e202302394. [PMID: 38925865 PMCID: PMC11208737 DOI: 10.26508/lsa.202302394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 06/15/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Genome-wide association studies have identified over 200 genetic loci associated with inflammatory bowel disease; however, the mechanism of such a large amount of susceptibility genes remains uncertain. In this study, we integrated bioinformatics analysis and two independent single-cell transcriptome datasets to investigate the expression network of 232 susceptibility genes in Crohn's disease (CD) patients and healthy controls. The study revealed that most of the susceptibility genes are specifically and strictly expressed in the monocytes of the human intestinal tract. The susceptibility genes established a network within the monocytes of health control. The robustness of a gene network may prevent disease onset that is influenced by the genetic and environmental alteration in the expression of susceptibility genes. In contrast, we showed a sparse network in pediatric/adult CD patients, suggesting the broken network contributed to the CD etiology. The network status of susceptibility genes at the single-cell level of monocytes provided novel insight into the etiology.
Collapse
Affiliation(s)
- Hankui Liu
- Hebei Industrial Technology Research Institute of Genomics in Maternal & Child Health, Clin Lab, BGI Genomics, Shijiazhuang, China
- BGI Genomics, Shenzhen, China
| | - Liping Guan
- Hebei Industrial Technology Research Institute of Genomics in Maternal & Child Health, Clin Lab, BGI Genomics, Shijiazhuang, China
- BGI Genomics, Shenzhen, China
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Xi Su
- BGI Genomics, Shenzhen, China
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Lijian Zhao
- Hebei Industrial Technology Research Institute of Genomics in Maternal & Child Health, Clin Lab, BGI Genomics, Shijiazhuang, China
- BGI Genomics, Shenzhen, China
- Hebei Medical University, Shijiazhuang, China
| | - Qing Shu
- Department of Gastroenterology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Jianguo Zhang
- Hebei Industrial Technology Research Institute of Genomics in Maternal & Child Health, Clin Lab, BGI Genomics, Shijiazhuang, China
- BGI Research, Shenzhen, China
- Hebei Medical University, Shijiazhuang, China
| |
Collapse
|
|
13
|
Tsokos GC. The immunology of systemic lupus erythematosus. Nat Immunol 2024; 25:1332-1343. [PMID: 39009839 DOI: 10.1038/s41590-024-01898-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/17/2024] [Indexed: 07/17/2024]
Abstract
Understanding the pathogenesis and clinical manifestations of systemic lupus erythematosus (SLE) has been a great challenge. Reductionist approaches to understand the nature of the disease have identified many pathogenetic contributors that parallel clinical heterogeneity. This Review outlines the immunological control of SLE and looks to experimental tools and approaches that are improving our understanding of the complex contribution of interacting genetics, environment, sex and immunoregulatory factors and their interface with processes inherent to tissue parenchymal cells. Efforts to advance precision medicine in the care of patients with SLE along with treatment strategies to correct the immune system hold hope and are also examined.
Collapse
Affiliation(s)
- George C Tsokos
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
14
|
Huang W, Jin T, Zheng W, Yin Q, Yan Q, Pan H, Xu C. Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases. J Autoimmun 2024; 145:103188. [PMID: 38458076 DOI: 10.1016/j.jaut.2024.103188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/14/2024] [Accepted: 02/18/2024] [Indexed: 03/10/2024]
Abstract
BACKGROUND Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. METHODS A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. RESULTS We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15-1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39-1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01-1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00-1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. CONCLUSIONS We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.
Collapse
MESH Headings
- Humans
- Lupus Erythematosus, Systemic/genetics
- Lupus Erythematosus, Systemic/epidemiology
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Hepatitis, Autoimmune/genetics
- Hepatitis, Autoimmune/epidemiology
- Liver Cirrhosis, Biliary/genetics
- Liver Cirrhosis, Biliary/epidemiology
- Liver Cirrhosis, Biliary/etiology
- Cholangitis, Sclerosing/genetics
- Cholangitis, Sclerosing/epidemiology
- Autoimmune Diseases/genetics
- Autoimmune Diseases/epidemiology
- Autoimmune Diseases/etiology
- Odds Ratio
- Risk Factors
- Liver Diseases/genetics
- Liver Diseases/epidemiology
- Liver Diseases/etiology
Collapse
Affiliation(s)
- Wei Huang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
| | - Tianyu Jin
- Department of Rehabilitation Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Wei Zheng
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
| | - Qiaoqiao Yin
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
| | - Qiqi Yan
- Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Hongying Pan
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
| | - Chengan Xu
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
| |
Collapse
|
|
15
|
Hosomi Y, Okamura T, Sakai K, Yuge H, Yoshimura T, Majima S, Okada H, Senmaru T, Ushigome E, Nakanishi N, Satoh T, Akira S, Hamaguchi M, Fukui M. IL-33 Reduces Saturated Fatty Acid Accumulation in Mouse Atherosclerotic Foci. Nutrients 2024; 16:1195. [PMID: 38674885 PMCID: PMC11054828 DOI: 10.3390/nu16081195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/14/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.
Collapse
Affiliation(s)
- Yukako Hosomi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Takuro Okamura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Kimiko Sakai
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Hiroki Yuge
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Takashi Yoshimura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Saori Majima
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Hiroshi Okada
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Takafumi Senmaru
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Emi Ushigome
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Naoko Nakanishi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Takashi Satoh
- Department of Immune Regulation, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan;
| | - Shizuo Akira
- Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita 565-0871, Japan;
- Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; (Y.H.); (T.O.); (K.S.); (H.Y.); (T.Y.); (S.M.); (H.O.); (T.S.); (E.U.); (N.N.); (M.F.)
| |
Collapse
|
|
16
|
Tchitchek N, Binvignat M, Roux A, Pitoiset F, Dubois J, Marguerit G, Saadoun D, Cacoub P, Sellam J, Berenbaum F, Hartemann A, Amouyal C, Lorenzon R, Mariotti-Ferrandiz E, Rosenzwajg M, Klatzmann D. Deep immunophenotyping reveals that autoimmune and autoinflammatory disorders are spread along two immunological axes capturing disease inflammation levels and types. Ann Rheum Dis 2024; 83:638-650. [PMID: 38182406 PMCID: PMC11041612 DOI: 10.1136/ard-2023-225179] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 12/17/2023] [Indexed: 01/07/2024]
Abstract
OBJECTIVES Based on genetic associations, McGonagle and McDermott suggested a classification of autoimmune and autoinflammatory diseases as a continuum ranging from purely autoimmune to purely autoinflammatory diseases and comprising diseases with both components. We used deep immunophenotyping to identify immune cell populations and molecular targets characterising this continuum. METHODS We collected blood from 443 patients with one of 15 autoimmune or autoinflammatory diseases and 71 healthy volunteers. Deep phenotyping was performed using 13 flow cytometry panels characterising over 600 innate and adaptive cell populations. Unsupervised and supervised analyses were conducted to identify disease clusters with their common and specific cell parameters. RESULTS Unsupervised clustering categorised these diseases into five clusters. Principal component analysis deconvoluted this clustering into two immunological axes. The first axis was driven by the ratio of LAG3+ to ICOS+ in regulatory T lymphocytes (Tregs), and segregated diseases based on their inflammation levels. The second axis was driven by activated Tregs and type 3 innate lymphoid cells (ILC3s), and segregated diseases based on their types of affected tissues. We identified a signature of 23 cell populations that accurately characterised the five disease clusters. CONCLUSIONS We have refined the monodimensional continuum of autoimmune and autoinflammatory diseases as a continuum characterised by both disease inflammation levels and targeted tissues. Such classification should be helpful for defining therapies. Our results call for further investigations into the role of the LAG3+/ICOS+ balance in Tregs and the contribution of ILC3s in autoimmune and autoinflammatory diseases. TRIAL REGISTRATION NUMBER NCT02466217.
Collapse
Affiliation(s)
- Nicolas Tchitchek
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - Marie Binvignat
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- INSERM U938, Rheumatology Department, Saint-Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Alexandra Roux
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - Fabien Pitoiset
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - Johanna Dubois
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - Gwendolyn Marguerit
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - David Saadoun
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
- Department of Internal Medicine and Clinical Immunology and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Reference Center for Autoinflammatory Disorders (CEREMAIA); Reference Center for Systemic Autoimmune Diseases, Paris, France
| | - Patrice Cacoub
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
- Department of Internal Medicine and Clinical Immunology and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Reference Center for Autoinflammatory Disorders (CEREMAIA); Reference Center for Systemic Autoimmune Diseases, Paris, France
| | - Jérémie Sellam
- INSERM U938, Rheumatology Department, Saint-Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Francis Berenbaum
- INSERM U938, Rheumatology Department, Saint-Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Agnès Hartemann
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
- Diabetology-Metabolism Department, AP-HP, Institut Hospitalo-Universitaire de Cardiometabolisme et Nutrition (ICAN), Pitié-Salpêtrière-Charles Foix Hospital, Sorbonne Université, Paris, France
| | - Chloé Amouyal
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
- Diabetology-Metabolism Department, AP-HP, Institut Hospitalo-Universitaire de Cardiometabolisme et Nutrition (ICAN), Pitié-Salpêtrière-Charles Foix Hospital, Sorbonne Université, Paris, France
| | - Roberta Lorenzon
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - Encarnita Mariotti-Ferrandiz
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
- Institut Universitaire de France (IUF), Paris, France
| | - Michelle Rosenzwajg
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| | - David Klatzmann
- INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France
- Clinical Investigation Center for Biotherapies (CIC-BTi) and Immunology-Inflammation-Infectiology and Dermatology Department (3iD), Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière-Charles Foix Hospital, Paris, France
| |
Collapse
|
|
17
|
Kühnel I, Vogler I, Spreu J, Bonig H, Döring C, Steinle A. The activating receptor NKp65 is selectively expressed by human ILC3 and demarcates ILC3 from mature NK cells. Eur J Immunol 2024; 54:e2250318. [PMID: 38072999 DOI: 10.1002/eji.202250318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/05/2023] [Accepted: 12/07/2023] [Indexed: 02/27/2024]
Abstract
Innate lymphocytes comprise cytotoxic natural killer (NK) cells and tissue-resident innate lymphoid cells (ILC) that are subgrouped according to their cytokine profiles into group 1 ILC (ILC1), ILC2, and ILC3. However, cell surface receptors unambiguously defining or specifically activating such ILC subsets are scarcely known. Here, we report on the physiologic expression of the human activating C-type lectin-like receptor (CTLR) NKp65, a high-affinity receptor for the CTLR keratinocyte-associated C-type lectin (KACL). Tracking rare NKp65 transcripts in human blood, we identify ILC3 to selectively express NKp65. NKp65 expression not only demarcates "bona fide" ILC3 from likewise RORγt-expressing ILC precursors and lymphoid tissue inducer cells but also from mature NK cells which acquire the NKp65-relative NKp80 during a Notch-dependent differentiation from NKp65+ precursor cells. Hence, ILC3 and NK cells mutually exclusively and interdependently express the genetically coupled sibling receptors NKp65 and NKp80. Much alike NKp80, NKp65 promotes cytotoxicity by innate lymphocytes which may become relevant during pathophysiological reprogramming of ILC3. Altogether, we report the selective expression of the activating immunoreceptor NKp65 by ILC3 demarcating ILC3 from mature NK cells and endowing ILC3 with a dedicated immunosensor for the epidermal immune barrier.
Collapse
Affiliation(s)
- Ines Kühnel
- Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany
- Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany
| | - Isabel Vogler
- Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany
| | - Jessica Spreu
- Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany
| | - Halvard Bonig
- Institute for Transfusion Medicine and Immunohematology, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany
- German Red Cross Blood Service Baden-Württemberg-Hessen, Frankfurt am Main, Germany
| | - Claudia Döring
- Dr. Senckenbergisches Institute of Pathology, Goethe University Hospital Frankfurt am Main, Frankfurt am Main, Germany
| | - Alexander Steinle
- Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany
| |
Collapse
|
|
18
|
Stosik M, Tokarz-Deptuła B, Deptuła W. Innate lymphoid cells (ILCs) in teleosts against data on ILCs in humans. FISH & SHELLFISH IMMUNOLOGY 2024; 146:109415. [PMID: 38296004 DOI: 10.1016/j.fsi.2024.109415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/26/2024] [Accepted: 01/28/2024] [Indexed: 02/13/2024]
Abstract
It is assumed that cells corresponding to innate lymphoid cells (ILCs) in humans, in addition to lymphoid tissue inducer cells (LTi), are also found in teleosts. In this systematic group of organisms, however, they are a poorly understood cell population. In contrast to the data on ILCs in humans, which also remain incomplete despite advanced research, in teleosts, these cells require much more attention. ILCs in teleosts have been presented as cells that may be evolutionary precursors of NK cells or ILCs identified in mammals, including humans. It is a highly heterogeneous group of cells in both humans and fish and their properties, as revealed by studies in humans, are most likely to remain strictly dependent on the location of these cells and the physiological state of the individual from which they originate. They form a bridge between innate and adaptive immunity. The premise of this paper is to review the current knowledge of ILCs in teleosts, taking into account data on similar cells in humans. A review of the knowledge concerning these particular cells, elements of innate immunity mechanisms as equivalent to, or perhaps dominant over, adaptive immunity mechanisms in teleosts, as presented, may inspire the need for further research.
Collapse
Affiliation(s)
- Michał Stosik
- Institute of Biological Sciences, University of Zielona Góra, Poland
| | | | - Wiesław Deptuła
- Institute of Veterinary Medicine, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, Poland
| |
Collapse
|
|
19
|
Li F, Liang Z, Zhong H, Hu X, Tang Z, Zhu C, Shen J, Han X, Lin R, Zheng R, Tang R, Peng H, Zheng X, Mo C, Chen P, Wang X, Wen Q, Li J, Xia X, Ye H, Qiu Y, Yu J, Fu D, Liu J, Wang R, Xie H, Guo Y, Li X, Fan J, Liu Q, Mao H, Chen W, Zhou Y. Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2302804. [PMID: 37915129 PMCID: PMC10724443 DOI: 10.1002/advs.202302804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 08/28/2023] [Indexed: 11/03/2023]
Abstract
Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.
Collapse
Affiliation(s)
- Feng Li
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Zhou Liang
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Haojie Zhong
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
- Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated Hospital, Shenzhen UniversityShenzhen518000China
| | - Xinrong Hu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Ziwen Tang
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Changjian Zhu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Jiani Shen
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Xu Han
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Ruoni Lin
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Ruilin Zheng
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Ruihan Tang
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Huajing Peng
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Xunhua Zheng
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Chengqiang Mo
- Department of UrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
| | - Peisong Chen
- Department of Laboratory MedicineThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
| | - Xin Wang
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Qiong Wen
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Jianbo Li
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Xi Xia
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Hongjian Ye
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Yagui Qiu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Jianwen Yu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Dongying Fu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Jiaqi Liu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Rong Wang
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Huixin Xie
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Yun Guo
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Xiaoyan Li
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Jinjin Fan
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Qinghua Liu
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Haiping Mao
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Wei Chen
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| | - Yi Zhou
- Department of NephrologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhou510080China
- NHC Key Laboratory of Clinical Nephrology (Sun Yat‐Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhou510080China
| |
Collapse
|
|
20
|
Jia H, Wan H, Zhang D. Innate lymphoid cells: a new key player in atopic dermatitis. Front Immunol 2023; 14:1277120. [PMID: 37908364 PMCID: PMC10613734 DOI: 10.3389/fimmu.2023.1277120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 09/25/2023] [Indexed: 11/02/2023] Open
Abstract
Atopic dermatitis (AD) is a common allergic inflammatory skin condition mainly caused by gene variants, immune disorders, and environmental risk factors. The T helper (Th) 2 immune response mediated by interleukin (IL)-4/13 is generally believed to be central in the pathogenesis of AD. It has been shown that innate lymphoid cells (ILCs) play a major effector cell role in the immune response in tissue homeostasis and inflammation and fascinating details about the interaction between innate and adaptive immunity. Changes in ILCs may contribute to the onset and progression of AD, and ILC2s especially have gained much attention. However, the role of ILCs in AD still needs to be further elucidated. This review summarizes the role of ILCs in skin homeostasis and highlights the signaling pathways in which ILCs may be involved in AD, thus providing valuable insights into the behavior of ILCs in skin homeostasis and inflammation, as well as new approaches to treating AD.
Collapse
Affiliation(s)
- Haiping Jia
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, China
| | - Huiying Wan
- Department of Dermatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Dingding Zhang
- Sichuan Provincial Key Laboratory for Genetic Disease, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| |
Collapse
|
|
21
|
Lu Z, Wang H, Gong Z, Guo P, Li C, Bi K, Li X, Chen Y, Pan A, Xu Y, Zhou P, Wei Z, Jiang H, Cao Y. The enrichment of Arg1 +ILC2s and ILCregs facilitates the progression of endometriosis: A preliminary study. Int Immunopharmacol 2023; 121:110421. [PMID: 37302364 DOI: 10.1016/j.intimp.2023.110421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/19/2023] [Accepted: 05/30/2023] [Indexed: 06/13/2023]
Abstract
Innate lymphoid cells (ILCs) are a kind of lymphocytes that reside in the tissue and have an essential function in the immune microenvironment. However, the relationship between endometriosis (EMS) and ILCs is complex and not fully understood. This study examines several groups of ILCs in the peripheral blood (PB), peritoneal fluid (PF) and endometrium of patients with EMS via flow cytometry. The study observed an increase in PB ILCs, particularly ILC2s and ILCregs subsets and Arg1+ILC2s in the EMS patients were highly activated. EMS patients had significantly higher levels of serum interleukin (IL)-10/33/25 compared to controls. We also found an elevation of Arg1+ILC2s in the PF and higher levels of ILC2s and ILCregs in ectopic endometrium compared with eutopic. Importantly, a positive correlation was observed between the enrichment of Arg1+ILC2s and ILCregs in the PB of EMS patients. The findings indicate that the involvement of Arg1+ILC2s and ILCregs fosters potentially endometriosis progression.
Collapse
Affiliation(s)
- Zhimin Lu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Hao Wang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Zhangyun Gong
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Peipei Guo
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Caihua Li
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Kaihuan Bi
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Xuqing Li
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Ya Chen
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Anan Pan
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Yuping Xu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Ping Zhou
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Zhaolian Wei
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China
| | - Huanhuan Jiang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
| | - Yunxia Cao
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Wanshui Road No.120, Hefei 230000, China; NHC Key Laboratory of Study on ABNORMAL gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
| |
Collapse
|
|
22
|
Hu C, Liao S, Lv L, Li C, Mei Z. Intestinal Immune Imbalance is an Alarm in the Development of IBD. Mediators Inflamm 2023; 2023:1073984. [PMID: 37554552 PMCID: PMC10406561 DOI: 10.1155/2023/1073984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 07/06/2023] [Accepted: 07/08/2023] [Indexed: 08/10/2023] Open
Abstract
Immune regulation plays a crucial role in human health and disease. Inflammatory bowel disease (IBD) is a chronic relapse bowel disease with an increasing incidence worldwide. Clinical treatments for IBD are limited and inefficient. However, the pathogenesis of immune-mediated IBD remains unclear. This review describes the activation of innate and adaptive immune functions by intestinal immune cells to regulate intestinal immune balance and maintain intestinal mucosal integrity. Changes in susceptible genes, autophagy, energy metabolism, and other factors interact in a complex manner with the immune system, eventually leading to intestinal immune imbalance and the onset of IBD. These events indicate that intestinal immune imbalance is an alarm for IBD development, further opening new possibilities for the unprecedented development of immunotherapy for IBD.
Collapse
Affiliation(s)
- Chunli Hu
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Shengtao Liao
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Lin Lv
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Chuanfei Li
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Zhechuan Mei
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| |
Collapse
|
|
23
|
Rizzi A, Di Gioacchino M, Gammeri L, Inchingolo R, Chini R, Santilli F, Nucera E, Gangemi S. The Emerging Role of Innate Lymphoid Cells (ILCs) and Alarmins in Celiac Disease: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications. Cells 2023; 12:1910. [PMID: 37508573 PMCID: PMC10378400 DOI: 10.3390/cells12141910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/16/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Celiac disease (CD) is an intestinal disease that develops in genetically predisposed individuals and is triggered by the ingestion of gluten. CD was considered a Th1-disease. Today, the role of Th17, IL-21, and IL-17A lymphocytes is well known. Inflammation is regulated by the activity of gluten-specific CD4+ T lymphocytes that produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-21, perpetuating the Th1 response. These cytokines determine an inflammatory state of the small intestine, with consequent epithelial infiltration of lymphocytes and an alteration of the architecture of the duodenal mucosa. B cells produce antibodies against tissue transglutaminase and against deamidated gliadin. Although the role of the adaptive immune response is currently known, the evidence about the role of innate immunity cells is still poorly understood. Epithelial damage determines the release of damage-associated molecular patterns (DAMPs), also known as alarmins. Together with the intestinal epithelial cells and the type 1 innate lymphoid cells (ILC1s), alarmins like TSLP, IL-33, and HMGB1 could have a fundamental role in the genesis and maintenance of inflammation. Our study aims to evaluate the evidence in the literature about the role of ILCs and alarmins in celiac disease, evaluating the possible future diagnostic and therapeutic implications.
Collapse
Affiliation(s)
- Angela Rizzi
- UOSD Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Mario Di Gioacchino
- Institute for Clinical Immunotherapy and Advanced Biological Treatments, 65100 Pescara, Italy
- Center for Advanced Studies and Technology, G. d'Annunzio University, 66100 Chieti, Italy
| | - Luca Gammeri
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
| | - Riccardo Inchingolo
- Pulmonary Medicine Unit, Department of Neurosciences, Sense Organs and Thorax, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Raffaella Chini
- UOSD Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Santilli
- Center for Advanced Studies and Technology, G. d'Annunzio University, 66100 Chieti, Italy
| | - Eleonora Nucera
- UOSD Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Sebastiano Gangemi
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
| |
Collapse
|
|
24
|
Schorr C, Krishnan MS, Capitano M. Deficits in our understanding of natural killer cell development in mouse and human. Curr Opin Hematol 2023; 30:106-116. [PMID: 37074304 PMCID: PMC10239331 DOI: 10.1097/moh.0000000000000765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023]
Abstract
PURPOSE OF REVIEW Natural killer (NK) cells are a type of immune cell that play a crucial role in the defense against cancer and viral infections. The development and maturation of NK cells is a complex process, involving the coordination of various signaling pathways, transcription factors, and epigenetic modifications. In recent years, there has been a growing interest in studying the development of NK cells. In this review, we discuss the field's current understanding of the journey a hematopoietic stem cell takes to become a fully mature NK cell and detail the sequential steps and regulation of conventional NK leukopoiesis in both mice and humans. RECENT FINDINGS Recent studies have highlighted the significance of defining NK development stages. Several groups report differing schema to identify NK cell development and new findings demonstrate novel ways to classify NK cells. Further investigation of NK cell biology and development is needed, as multiomic analysis reveals a large diversity in NK cell development pathways. SUMMARY We provide an overview of current knowledge on the development of NK cells, including the various stages of differentiation, the regulation of development, and the maturation of NK cells in both mice and humans. A deeper understanding of NK cell development has the potential to provide insights into new therapeutic strategies for the treatment of diseases such as cancer and viral infections.
Collapse
Affiliation(s)
- Christopher Schorr
- Indiana University School of Medicine, Indianapolis, IN
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN
| | - Maya Shraddha Krishnan
- Indiana University School of Medicine, Indianapolis, IN
- Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN
| | - Maegan Capitano
- Indiana University School of Medicine, Indianapolis, IN
- Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN
| |
Collapse
|
|
25
|
Zeng H, Zhuang Y, Li X, Yin Z, Huang X, Peng H. Exploring the potential common denominator pathogenesis of system lupus erythematosus with COVID-19 based on comprehensive bioinformatics analysis. Front Immunol 2023; 14:1179664. [PMID: 37426642 PMCID: PMC10325730 DOI: 10.3389/fimmu.2023.1179664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 06/06/2023] [Indexed: 07/11/2023] Open
Abstract
Objective Evidences show that there may be a link between SLE and COVID-19. The purpose of this study is to screen out the diagnostic biomarkers of systemic lupus erythematosus (SLE) with COVID-19 and explore the possible related mechanisms by the bioinformatics approach. Methods SLE and COVID-19 datasets were extracted separately from the NCBI Gene Expression Omnibus (GEO) database. The limma package in R was used to obtain the differential genes (DEGs). The protein interaction network information (PPI) and core functional modules were constructed in the STRING database using Cytoscape software. The hub genes were identified by the Cytohubba plugin, and TF-gene together with TF-miRNA regulatory networks were constructed via utilizing the Networkanalyst platform. Subsequently, we generated subject operating characteristic curves (ROC) to verify the diagnostic capabilities of these hub genes to predict the risk of SLE with COVID-19 infection. Finally, a single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration. Results A total of 6 common hub genes (CDC6, PLCG1, KIF15, LCK, CDC25C, and RASGRP1) were identified with high diagnostic validity. These gene functional enrichments were mainly involved in cell cycle, and inflammation-related pathways. Compared to the healthy controls, abnormal infiltration of immune cells was found in SLE and COVID-19, and the proportion of immune cells linked to the 6 hub genes. Conclusion Our research logically identified 6 candidate hub genes that could predict SLE complicated with COVID-19. This work provides a foothold for further study of potential pathogenesis in SLE and COVID-19.
Collapse
Affiliation(s)
- Huiqiong Zeng
- Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Futian District, Shenzhen, Guangdong, China
| | - Yu Zhuang
- Department of Rheumatology and Immunology, Huizhou Central People’s Hospital, Huizhou, Guangdong, China
| | - Xiaojuan Li
- Department of Public Health, Shenzhen Hospital of Southern Medical University, Shenzhen, China
| | - Zhihua Yin
- Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Futian District, Shenzhen, Guangdong, China
| | - Xia Huang
- Department of Xi Yuan Community Health Service Center, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Haiyan Peng
- Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Futian District, Shenzhen, Guangdong, China
| |
Collapse
|
|
26
|
Borgia F, Li Pomi F, Alessandrello C, Vaccaro M, Gangemi S. Potential Role of Innate Lymphoid Cells in the Pathogenesis and Treatment of Skin Diseases. J Clin Med 2023; 12:jcm12083043. [PMID: 37109379 PMCID: PMC10144013 DOI: 10.3390/jcm12083043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/17/2023] [Accepted: 04/21/2023] [Indexed: 04/29/2023] Open
Abstract
Group 2 innate lymphoid cells (ILC2s) are lymphoid cells that are resident in mucosal tissues, especially the skin, which, once stimulated by epithelial cell-derived cytokines, release IL-5, IL-13, and IL-4, as the effectors of type 2 immune responses. This research aims to evaluate the role of ILC2s in the pathogenesis of skin diseases, with a particular focus on inflammatory cutaneous disorders, in order to also elucidate potential therapeutic perspectives. The research has been conducted in articles, excluding reviews and meta-analyses, on both animals and humans. The results showed that ILC2s play a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and severity, while a potential antimelanoma role is emerging from the new research. Future perspectives could include the development of new antibodies targeting or stimulating ILC2 release. This evidence could add a new therapeutic approach to inflammatory cutaneous conditions, including allergic ones.
Collapse
Affiliation(s)
- Francesco Borgia
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, 98125 Messina, Italy
| | - Federica Li Pomi
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, 98125 Messina, Italy
| | - Clara Alessandrello
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
| | - Mario Vaccaro
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, 98125 Messina, Italy
| | - Sebastiano Gangemi
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
| |
Collapse
|
|
27
|
Del Vescovo S, Venerito V, Iannone C, Lopalco G. Uncovering the Underworld of Axial Spondyloarthritis. Int J Mol Sci 2023; 24:6463. [PMID: 37047435 PMCID: PMC10095023 DOI: 10.3390/ijms24076463] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/28/2023] [Accepted: 03/28/2023] [Indexed: 04/14/2023] Open
Abstract
Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.
Collapse
Affiliation(s)
- Sergio Del Vescovo
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, 70124 Bari, Italy
| | - Vincenzo Venerito
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, 70124 Bari, Italy
| | - Claudia Iannone
- Division of Clinical Rheumatology, ASST Gaetano Pini-CTO Institute, 20122 Milan, Italy
| | - Giuseppe Lopalco
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Polyclinic Hospital, University of Bari, 70124 Bari, Italy
| |
Collapse
|
|
28
|
Laufer Britva R, Keren A, Bertolini M, Ullmann Y, Paus R, Gilhar A. Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata. eLife 2023; 12:80768. [PMID: 36930216 PMCID: PMC10023162 DOI: 10.7554/elife.80768] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 02/22/2023] [Indexed: 03/11/2023] Open
Abstract
Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease.
Collapse
Affiliation(s)
- Rimma Laufer Britva
- Skin Research Laboratory, Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyHaifaIsrael
- Department of Dermatology, Rambam Health Care CampusHaifaIsrael
| | - Aviad Keren
- Skin Research Laboratory, Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyHaifaIsrael
| | | | - Yehuda Ullmann
- Department of Plastic Surgery, Rambam Medical CenterHaifaIsrael
| | - Ralf Paus
- Monasterium LaboratoryMünsterGermany
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, Miller School of Medicine, University of MiamiMiamiUnited States
- CUTANEONHamburgGermany
| | - Amos Gilhar
- Skin Research Laboratory, Rappaport Faculty of Medicine, Technion – Israel Institute of TechnologyHaifaIsrael
| |
Collapse
|
|
29
|
Matsumoto K, Suzuki K, Yasuoka H, Hirahashi J, Yoshida H, Magi M, Noguchi-Sasaki M, Kaneko Y, Takeuchi T. Longitudinal monitoring of circulating immune cell phenotypes in anti-neutrophil cytoplasmic antibody-associated vasculitis. Autoimmun Rev 2023; 22:103271. [PMID: 36627064 DOI: 10.1016/j.autrev.2023.103271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 01/05/2023] [Indexed: 01/09/2023]
Abstract
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a necrotizing multiorgan autoimmune disease that affects small- to medium-sized blood vessels. Despite the improvements in treatments, half of the patients with AAV still experience disease relapses. In this review, we focus on peripheral leukocyte properties and phenotypes in patients with AAV. In particular, we explore longitudinal changes in circulating immune cell phenotypes during the active phase of the disease and treatment. The numbers and phenotypes of leukocytes in peripheral blood were differs between AAV and healthy controls, AAV in active versus inactive phase, AAV in treatment responders versus non-responders, and AAV with and without severe infection. Therefore, biomarkers detected in peripheral blood immune cells may be useful for longitudinal monitoring of disease activity in AAV.
Collapse
Affiliation(s)
- Kotaro Matsumoto
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
| | - Katsuya Suzuki
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hidekata Yasuoka
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Division of Rheumatology, Department of Internal Medicine, Fujita Health University School of Medicine, Aichi, Japan
| | - Junichi Hirahashi
- Center for General Medicine Education, Keio University School of Medicine, Tokyo, Japan
| | | | - Mayu Magi
- Chugai Pharmaceutical Co. Ltd., Kanagawa, Japan
| | | | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
30
|
Verdier J, Fayet OM, Hemery E, Truffault F, Pinzón N, Demeret S, Behin A, Fadel E, Guihaire J, Corneau A, Blanc C, Berrih-Aknin S, Le Panse R. Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells. Front Immunol 2023; 14:1083218. [PMID: 36793723 PMCID: PMC9922723 DOI: 10.3389/fimmu.2023.1083218] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 01/04/2023] [Indexed: 01/31/2023] Open
Abstract
Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.
Collapse
Affiliation(s)
- Julien Verdier
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| | - Odessa-Maud Fayet
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| | - Edouard Hemery
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| | - Frédérique Truffault
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| | - Natalia Pinzón
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| | - Sophie Demeret
- APHP, Assistance Publique - Hopitaux de Paris, Paris, France
| | - Anthony Behin
- AP-HP, Referral Center for Neuromuscular Disorders, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France
| | - Elie Fadel
- Marie Lannelongue Hospital, Paris-Sud University, Le Plessis-Robinson, France
| | - Julien Guihaire
- Marie Lannelongue Hospital, Paris-Sud University, Le Plessis-Robinson, France
| | - Aurélien Corneau
- Plateforme de Cytométrie de la Pitié-Salpétrière (CyPS), UMS037-PASS, Sorbonne Université-Faculté de Médecine, Paris, France
| | - Catherine Blanc
- Plateforme de Cytométrie de la Pitié-Salpétrière (CyPS), UMS037-PASS, Sorbonne Université-Faculté de Médecine, Paris, France
| | - Sonia Berrih-Aknin
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| | - Rozen Le Panse
- Sorbonne University, INSERM, Institute of Myology, Center of Research in Myology, Paris, France
| |
Collapse
|
|
31
|
Zeng Q, Zeng Y, Xiao H, Li J, Yang C, Luo R, Liu W, Wen Y. Interleukin-37b Suppressed ILC2s in Children with Allergic Rhinitis. Mediators Inflamm 2023; 2023:1572891. [PMID: 37091906 PMCID: PMC10121347 DOI: 10.1155/2023/1572891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 03/26/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023] Open
Abstract
Background Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear. Methods We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18Rα, and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA. Results We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18Rα, and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years' SLIT, especially in the good response group. Conclusion Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR.
Collapse
Affiliation(s)
- Qingxiang Zeng
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
| | - Yinhui Zeng
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
| | - Haiqing Xiao
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
| | - Jinyuan Li
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
| | - Chao Yang
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
| | - Renzhong Luo
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
| | - Wenlong Liu
- Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, China
- Department of Otolaryngology, Liuzhou hospital of Guangzhou Women and Children's Medical Center, Guangxi 545001, China
| | - Yanhui Wen
- The Third People's Hospital of Dongguan, Dongguan Songshan Lake Center Hospital, Dongguan, China
| |
Collapse
|
|
32
|
Schindler V, Venhoff N. Eosinophile Granulomatose mit Polyangiitis – ein
Übersichtsartikel. AKTUEL RHEUMATOL 2022. [DOI: 10.1055/a-1947-5254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
ZusammenfassungDie eosinophile Granulomatose mit Polyangiitis (EGPA) ist eine seltene Form der
ANCA-assoziierten Vaskulitiden (AAV) aus der Gruppe der
Kleingefäßvaskulitiden. Sie ist definiert als eine Vaskulitis
kleiner und mittelgroßer Gefäße mit
granulomatöser Entzündung sowie Blut- und Gewebseosinophilie.
Fast alle Patienten haben allergische Symptome mit Asthma bronchiale und
rhinosinusitischen Beschwerden. Das sonstige klinische Spektrum variiert je nach
Lokalisation, Schweregrad und Art der Krankheitsmanifestation. Durch die
eosinophile Infiltration und Inflammation kann es zu Rhinosinusitis,
Pneumonitis, gastrointestinaler Beteiligung und Kardiomyopathie kommen.
Insbesondere Letztere ist mit einer schlechteren Prognose assoziiert. Als
nekrotisierende pauci-immune Kleingefäßvaskulitis kann die EGPA,
ähnlich wie die anderen AAV, pulmonale Infiltrate mit alveolärer
Hämorrhagie, eine Glomerulonephritis, kutane Vaskulitis mit Purpura,
sowie zentrale und periphere neurologische Schädigungen verursachen. Das
Auftreten perinukleärer ANCA (pANCA), mit Spezifität gegen die
Myeloperoxidase (MPO) wird in etwa einem Drittel der Fälle beobachtet,
ist allerdings nicht spezifisch für die EGPA. MPO-ANCA-positive
Patienten haben häufiger eine periphere neurologische Beteiligung und
eine Glomerulonephritis, während ANCA-negative Patienten
häufiger eine kardiale und pulmonale Beteiligung aufweisen. Eine
differentialdiagnostische Herausforderung im klinischen Alltag stellt die
Abgrenzung zum hypereosinophilen Syndrom (HES) dar. Das Therapiekonzept der EGPA
hängt davon ab, ob der Schweregrad der Erkrankung potentiell Organ- oder
lebensbedrohlich ist. Bei schweren Formen der EGPA werden in der Akuttherapie
hauptsächlich Glukokortikoide in Kombination mit Cyclophosphamid
eingesetzt. Rituximab wird mittlerweile als alternative Behandlungsoption in den
Leitlinien genannt. Zur Remissionserhaltung stehen verschiedene immunsuppressive
Therapien zur Verfügung. Bei EGPA ohne schwere Organbeteiligung ist die
IL-5 Blockade mit Mepolizumab zugelassen.
Collapse
Affiliation(s)
- Viktoria Schindler
- Klinik für Rheumatologie und Klinische Immunologie, Department
Innere Medizin, Universitätsklinikum Freiburg, Freiburg,
Germany
| | - Nils Venhoff
- Klinik für Rheumatologie und Klinische Immunologie, Department
Innere Medizin, Universitätsklinikum Freiburg, Freiburg,
Germany
| |
Collapse
|
|
33
|
Nii T, Fukushima K, Kida H. Specific targeting of lung ILC2s via NRP1 in pulmonary fibrosis. Cell Mol Immunol 2022; 19:869-871. [PMID: 35459852 PMCID: PMC9338289 DOI: 10.1038/s41423-022-00867-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/05/2022] [Indexed: 11/09/2022] Open
Affiliation(s)
- Takuro Nii
- Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Osaka, Japan
| | - Kiyoharu Fukushima
- Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Osaka, Japan
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan
- Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center (WPI-IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan
- Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Osaka, 565-0871, Japan
- Global Center for Medical Engineering and Informatics, 2-2 Yamadaoka, Suita, Osaka, Japan
| | - Hiroshi Kida
- Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Osaka, Japan.
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
| |
Collapse
|
|
34
|
Zhang HM, Chen XJ, Li SP, Zhang JM, Sun J, Zhou LX, Zhou GP, Cui B, Sun LY, Zhu ZJ. ILC2s expanded by exogenous IL-33 regulate CD45+CD11b+F4/80high macrophage polarization to alleviate hepatic ischemia-reperfusion injury. Front Immunol 2022; 13:869365. [PMID: 35967407 PMCID: PMC9372719 DOI: 10.3389/fimmu.2022.869365] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 07/06/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.
Collapse
Affiliation(s)
- Hai-Ming Zhang
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Xiao-Jie Chen
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Shi-Peng Li
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Jin-Ming Zhang
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Jie Sun
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Liu-Xin Zhou
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Guang-Peng Zhou
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Bin Cui
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
| | - Li-Ying Sun
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
- Department of Critical Liver Disease, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- *Correspondence: Li-Ying Sun, ; Zhi-Jun Zhu,
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China
- *Correspondence: Li-Ying Sun, ; Zhi-Jun Zhu,
| |
Collapse
|
|
35
|
Allegra A, Casciaro M, Lo Presti E, Musolino C, Gangemi S. Harnessing Unconventional T Cells and Innate Lymphoid Cells to Prevent and Treat Hematological Malignancies: Prospects for New Immunotherapy. Biomolecules 2022; 12:biom12060754. [PMID: 35740879 PMCID: PMC9221132 DOI: 10.3390/biom12060754] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/21/2022] [Accepted: 05/26/2022] [Indexed: 11/18/2022] Open
Abstract
Unconventional T cells and innate lymphoid cells (ILCs) make up a heterogeneous set of cells that characteristically show prompt responses toward specific antigens. Unconventional T cells recognize non-peptide antigens, which are bound and presented by diverse non-polymorphic antigen-presenting molecules and comprise γδ T cells, MR1-restricted mucosal-associated invariant T cells (MAITs), and natural killer T cells (NKTs). On the other hand, ILCs lack antigen-specific receptors and act as the innate counterpart to the T lymphocytes found in the adaptive immune response. The alteration of unconventional T cells and ILCs in frequency and functionality is correlated with the onset of several autoimmune diseases, allergy, inflammation, and tumor. However, depending on the physio-pathological framework, unconventional T cells may exhibit either protective or pathogenic activity in a range of neoplastic diseases. Nonetheless, experimental models and clinical studies have displayed that some unconventional T cells are potential therapeutic targets, as well as prognostic and diagnostic markers. In fact, cell-mediated immune response in tumors has become the focus in immunotherapy against neoplastic disease. This review concentrates on the present knowledge concerning the function of unconventional T cell sets in the antitumor immune response in hematological malignancies, such as acute and chronic leukemia, multiple myeloma, and lymphoproliferative disorders. Moreover, we discuss the possibility that modulating the activity of unconventional T cells could be useful in the treatment of hematological neoplasms, in the prevention of specific conditions (such as graft versus host disease), and in the formulation of an effective anticancer vaccine therapy. The exact knowledge of the role of these cells could represent the prerequisite for the creation of a new form of immunotherapy for hematological neoplasms.
Collapse
Affiliation(s)
- Alessandro Allegra
- Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, Division of Hematology, University of Messina, 98125 Messina, Italy; (A.A.); (C.M.)
| | - Marco Casciaro
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy;
- Correspondence: ; Tel.: +39-090-221-2013
| | - Elena Lo Presti
- National Research Council (CNR)—Institute for Biomedical Research and Innovation (IRIB), 90146 Palermo, Italy;
| | - Caterina Musolino
- Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, Division of Hematology, University of Messina, 98125 Messina, Italy; (A.A.); (C.M.)
| | - Sebastiano Gangemi
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy;
| |
Collapse
|