• Children
• Cytokines
• DNA damage
• Oxidative stress
• Pesticides

• Humans
• Oxidative Stress/drug effects
• Child
• DNA Damage
• Male
• Pesticides/toxicity
• Female
• Environmental Exposure/adverse effects
• 8-Hydroxy-2'-Deoxyguanosine/urine
• Interleukin-8/blood
• Interleukin-8/genetics
• Malondialdehyde/blood
• Lipid Peroxidation/drug effects
• Environmental Pollutants/toxicity
• Environmental Pollutants/urine

• Graves’ disease
• flow cytometry
• innate immunity
• natural killer cells
• pathogenesis

• Humans
• Killer Cells, Natural/immunology
• Killer Cells, Natural/metabolism
• Graves Disease/immunology
• Graves Disease/metabolism
• Graves Disease/blood
• Male
• Female
• Adult
• Middle Aged
• Cell Degranulation
• Case-Control Studies
• Cytokines/metabolism
• Aged
• Flow Cytometry

• Vitamin D
• acquired immunity
• autoimmune disorders
• autoimmunity
• innate immunity

• Humans
• Vitamin D/metabolism
• Immunity, Innate
• Vitamins
• Autoimmune Diseases
• Adaptive Immunity

Studies investigating the immunopathology of multiple sclerosis (MS) have largely focused on adaptive T and B lymphocytes. However, in recent years there has been an increased interest in the contribution of innate immune cells, amongst which the natural killer (NK) cells. Apart from their canonical role of controlling viral infections, cell stress and malignancies, NK cells are increasingly being recognized for their modulating effect on the adaptive immune system, both in health and autoimmune disease. From different lines of research there is now evidence that NK cells contribute to MS immunopathology. In this review, we provide an overview of studies that have investigated the role of NK cells in the pathogenesis of MS by use of the experimental autoimmune encephalomyelitis (EAE) animal model, MS genetics or through ex vivo and in vitro work into the immunology of MS patients. With the advent of modern hypothesis-free technologies such as single-cell transcriptomics, we are exposing an unexpected NK cell heterogeneity, increasingly blurring the boundaries between adaptive and innate immunity. We conclude that unravelling this heterogeneity, as well as the mechanistic link between innate and adaptive immune cell functions will lay the foundation for the use of NK cells as prognostic tools and therapeutic targets in MS and a myriad of other currently uncurable autoimmune disorders.

• autoimmune disorders
• experimental autoimmune encephalomyelitis (EAE)
• immune cell heterogeneity
• multiple sclerosis
• multiple sclerosis genetics
• natural killer (NK) cells

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (P_FDR = 2.25 × 10⁻¹¹⁵; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (P_FDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (P_FDR = 1.45 × 10⁻³³; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

• AS
• HLA-B27
• MICA
• soluble MICA
• syndesmophyte

• R21 AI149395 NIAID NIH HHS

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week’s GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.

• VKH
• autoimmunity, cytokine
• immunopathogenesis
• lymphocyte subsets
• monocytes

• Autoantibodies
• Autoimmunity/genetics
• Bayes Theorem
• Diabetes Mellitus, Type 1/genetics
• Disease Progression
• Gene Regulatory Networks
• Genetic Predisposition to Disease
• Humans
• Islets of Langerhans
• Prospective Studies

• U01 DK063821 NIDDK NIH HHS
• UC4 DK063863 NIDDK NIH HHS
• 0406/Z/14/A Wellcome Trust
• U01 DK063861 NIDDK NIH HHS
• U01 DK063790 NIDDK NIH HHS
• UL1 TR001082 NCATS NIH HHS
• Wellcome Trust
• UL1 TR000064 NCATS NIH HHS
• HHSN267200700014C NLM NIH HHS
• U01 DK063836 NIDDK NIH HHS
• U01 DK063829 NIDDK NIH HHS
• 200871/Z/16/Z Wellcome Trust
• U01 DK063865 NIDDK NIH HHS
• UC4 DK095300 NIDDK NIH HHS
• UC4 DK063861 NIDDK NIH HHS
• UC4 DK063829 NIDDK NIH HHS
• UC4 DK063821 NIDDK NIH HHS
• UC4 DK117483 NIDDK NIH HHS
• UC4 DK063836 NIDDK NIH HHS
• UC4 DK112243 NIDDK NIH HHS
• UC4 DK063865 NIDDK NIH HHS
• U01 DK063863 NIDDK NIH HHS
• UC4 DK106955 NIDDK NIH HHS
• UC4 DK100238 NIDDK NIH HHS

The discovery that NK cells are able to specifically recognize cells lacking the expression of self‐MHC class I molecules provided the first insight into NK cell recognition of tumour cells. It started a flourishing field of NK cell research aimed at exploring the molecular nature of NK cell receptors involved in tumour cell recognition. While much of the important early work was conducted in murine experimental model systems, studies of human NK cells rapidly followed. Over the years, human NK cell research has swiftly progressed, aided by new detailed molecular information on human NK cell development, differentiation, molecular specificity, tissue heterogeneity and functional capacity. NK cells have also been studied in many different diseases aside from cancer, including viral diseases, autoimmunity, allergy and primary immunodeficiencies. These fields of research have all, indirectly or directly, provided further insights into NK cell‐mediated recognition of target cells and paved the way for the development of NK cell‐based immunotherapies for human cancer. Excitingly, NK cell‐based immunotherapy now opens up for novel strategies aimed towards treating malignant diseases, either alone or in combination with other drugs. Reviewed here are some personal reflections of select contributions leading up to the current state‐of‐the‐art in the field, with a particular emphasis on contributions from our own laboratory. This review is part of a series of articles on immunology in Scandinavia, published in conjunction with the 50th anniversary of the Scandinavian Society for Immunology.

• MHC class I
• NK cells
• cancer
• immunotherapy
• missing-self
• tumour immunity

Enteroviruses, especially group B coxsackieviruses (CV-B), have been associated with the development of chronic diseases such as type 1 diabetes (T1D). The pathological mechanisms that trigger virus-induced autoimmunity against islet antigens in T1D are not fully elucidated. Animal and human studies suggest that NK cells response to CV-B infection play a crucial role in the enteroviral pathogenesis of T1D. Indeed, CV-B-infected cells can escape from cytotoxic T cells recognition and destruction by inhibition of cell surface expression of HLA class I antigen through non-structural viral proteins, but they can nevertheless be killed by NK cells. Cytolytic activity of NK cells towards pancreatic beta cells persistently-infected with CV-B has been reported and defective viral clearance by NK cells of patients with T1D has been suggested as a mechanism leading to persistence of CV-B and triggering autoimmunity reported in these patients. The knowledge about host antiviral defense against CV-B infection is not only crucial to understand the susceptibility to virus-induced T1D but could also contribute to the design of new preventive or therapeutic approaches for individuals at risk for T1D or newly diagnosed patients.

• HLA class I
• NK cells
• enteroviruses
• persistence
• type 1 diabetes

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal NKp46⁺DX5⁺ NK cells, renal NKp46⁺DX5⁻ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• colorectal cancer
• flow cytometry
• immune function
• laparoscopy
• natural killer cells

• NK cells
• human immunology
• malaria

• Toll-like receptors
• activating NK receptors
• human natural killer cells
• innate immunity
• natural cytotoxicity receptors

• Adaptive Immunity/immunology
• Cell Communication/immunology
• Cytotoxicity, Immunologic/immunology
• Humans
• Immunity, Innate/immunology
• Immunologic Memory/immunology
• Killer Cells, Natural/immunology
• Lymphocytes/immunology
• Neoplasms/immunology
• Receptors, Natural Killer Cell/immunology

Currently published studies investigating association between the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and rheumatoid arthritis (RA) reported inconsistent and contradictory results. Hence, we aim to carry out this comprehensive meta-analysis of all eligible studies meeting the inclusion criteria to achieve precise and comprehensive relationships between genetic variations in KIR gene cluster and risk of RA.

Databases of Medline/PubMed and Scopus were searched to investigate case-control studies prior to May 2018. The associations between KIR gene polymorphisms and RA susceptibility were analyzed by computing the odds ratio (OR) and 95% confidence interval (95% CI) for each study.

A total of 11 comparative case-control studies involving 1847 RA patients and 2409 healthy individuals were included in this meta-analysis. Four significant associations of 2DL3 (OR = 0.591, 95% CI = 0.351–0.994; P = 0.047), 2DL5 (OR = 0.716, 95% CI = 0.601–0.853; P < 0.001), 2DS5 (OR = 0.623, 95% CI = 0.393–0.988; P = 0.045), and 3DL3 (OR = 0.324, 95% CI = 0.129–0.814; P = 0.016) genes with decreased RA risk were discovered in this meta-analysis. Although, other KIR receptors including 2DL1, 2DL2, 2DL4, 3DL1, 3DL2, 3DS1, 2DS1-2DS4, and two pseudo gens of 2DP1 and 3DP1 displayed no significant association with predisposition to RA.

These findings provide reliable evidence that 2DL3, 2DL5, 3DL3, and 2DS5 might have a potential protective role for RA.

• Arthritis
• Disease association
• Gene polymorphism
• Meta-analysis
• killer cell immunoglobulin-like receptor

Natural-killer group 2 member D (NKG2D) is a well-characterized activating receptor expressed by natural killer (NK) cells, NKT cells, activated CD8⁺ T cells, subsets of γδ⁺ T cells, and innate-like T cells. NKG2D recognizes multiple ligands (NKG2D-ligands) to mount an innate immune response against stressed, transformed, or infected cells. NKG2D-ligand surface expression is tightly restricted on healthy cells through transcriptional and post-transcriptional mechanisms, while transformed or infected cells express the ligands as a danger signal. Recent studies have revealed that unfolded protein response pathways during endoplasmic reticulum (ER) stress result in upregulation of ULBP-related protein via the protein kinase RNA-like ER kinase-activating factor 4-C/EBP homologous protein (PERK-ATF4-CHOP) pathway, which can be linked to the pathogenesis of autoimmune diseases. Transformed cells, however, possess mechanisms to escape NKG2D-mediated immune surveillance, such as upregulation of carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1), a negative regulator of NKG2D-ligands. In this review, we discuss mechanisms of NKG2D-ligand regulation, with a focus on newly discovered mechanisms that promote NKG2D-ligand expression on epithelial cells, including ER stress, and mechanisms that suppress NKG2D-ligand-mediated killing of cancer cells, namely by co-expression of CEACAM1.

• CEA-related cell adhesion molecule 1
• UL16 binding protein 1
• endoplasmic reticulum stress
• murine UL16-binding protein like transcript 1
• natural-killer group 2 member D
• natural-killer group 2 member D-ligand

• DNAM-1
• NK cells
• TIGIT
• autoimmune disease
• cancer
• immunotherapy

• Antigens, Differentiation, T-Lymphocyte/genetics
• Antigens, Differentiation, T-Lymphocyte/immunology
• Antineoplastic Agents, Immunological/therapeutic use
• Autoimmune Diseases/drug therapy
• Autoimmune Diseases/genetics
• Autoimmune Diseases/immunology
• Autoimmune Diseases/pathology
• Gene Expression Regulation
• Humans
• Immunotherapy/methods
• Killer Cells, Natural/drug effects
• Killer Cells, Natural/immunology
• Killer Cells, Natural/pathology
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/pathology
• Protein Binding
• Receptor Cross-Talk/immunology
• Receptors, Immunologic/agonists
• Receptors, Immunologic/antagonists & inhibitors
• Receptors, Immunologic/genetics
• Receptors, Immunologic/immunology
• Signal Transduction
• T-Lymphocytes, Cytotoxic/drug effects
• T-Lymphocytes, Cytotoxic/immunology
• T-Lymphocytes, Cytotoxic/pathology

• Barrier function
• Gut homeostasis
• Inflammatory bowel disease
• Innate immunity
• Microbiome
• Vitamin D

• Adaptive Immunity
• Gastrointestinal Microbiome/immunology
• Gastrointestinal Tract/microbiology
• Homeostasis
• Humans
• Immunity, Innate
• Inflammatory Bowel Diseases/immunology
• Intestines/immunology
• Vitamin D/immunology
• Vitamin D/metabolism

• Adolescent
• Blood Sedimentation
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• Hypersensitivity/blood
• Hypersensitivity/complications
• Hypersensitivity/immunology
• Lupus Erythematosus, Systemic/blood
• Lupus Erythematosus, Systemic/immunology
• Lymphocytes/metabolism
• Male
• Prognosis
• Prospective Studies
• Severity of Illness Index

• Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support

• Behçet’s disease
• NK1 cells
• NK2 cells
• cytokines
• cytotoxic activity
• natural killer cells

The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

• Immunohomeostasis
• Immunoprotection
• Immunoregeneration
• Inflammation
• Mesenchymal stem cells
• IMT504

• Autoimmunity
• DMARDs
• KIR genes
• pharmacogenetics
• treatment response

• Adaptive Immunity/immunology
• Animals
• Autoimmunity/immunology
• Evolution, Molecular
• Humans
• Hypersensitivity/immunology
• Immunity, Innate
• Immunologic Surveillance/immunology
• Killer Cells, Natural/cytology
• Killer Cells, Natural/immunology
• Macrophages/cytology
• Macrophages/immunology
• Monocytes/cytology
• Monocytes/immunology
• Neoplasms/immunology
• Phylogeny

• CX3CR1
• Chemokines
• EAE
• NK cells
• Neuroinflammation

• Cbl
• DAP10
• IFN-γ
• degranulation
• phosphoinositide-3-kinase

As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal “self” cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a “two-edged weapon” and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease.

• DNAM-1
• IL-2 receptor
• NK cells
• daclizumab
• multiple sclerosis

• Colitis
• Colon cancer
• Inflammation-associated colon cancer
• Inflammatory bowel disease
• Mouse models
• Vitamin D

• Animals
• Biomarkers/blood
• Colonic Neoplasms/blood
• Colonic Neoplasms/epidemiology
• Colonic Neoplasms/microbiology
• Colonic Neoplasms/prevention & control
• Dietary Supplements
• Gastrointestinal Microbiome
• Host-Pathogen Interactions
• Humans
• Inflammatory Bowel Diseases/blood
• Inflammatory Bowel Diseases/epidemiology
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/prevention & control
• Nutritional Status
• Protective Factors
• Risk Factors
• Signal Transduction
• Vitamin D/blood
• Vitamin D/therapeutic use
• Vitamin D Deficiency/blood
• Vitamin D Deficiency/drug therapy
• Vitamin D Deficiency/epidemiology
• Vitamin D Deficiency/microbiology

• R21 CA149995 NCI NIH HHS
• T32 DK007742 NIDDK NIH HHS
• 5T32DK007742-17 NIDDK NIH HHS
• R21 CA149995-01A1 NCI NIH HHS

• Eomes
• MICA
• MRL/MpJ
• MRL/lpr
• Rae
• T-bet

• CIA
• GlcNAc glycoconjugates
• clinical scoring
• cytokines
• humoral response

• Autoimmunity
• B cells
• Immunodeficiency
• Mucopolysaccharidoses
• NK cells

• Autoimmune disease
• Genetic association
• Killer immunoglobulin like receptor (KIR)
• Polymerase chain reaction-sequence specific primer (PCR-SSP)
• Rheumatoid arthritis (RA)

• humans
• natural killer cells
• cytotoxicity
• cd107a
• small molecule screening
• prestwick chemical library

• Antibodies, Monoclonal/pharmacology
• Antibody-Dependent Cell Cytotoxicity/immunology
• Cytotoxicity, Immunologic/immunology
• Flow Cytometry
• High-Throughput Screening Assays
• Humans
• Immunity, Cellular
• Immunologic Factors/pharmacology
• Killer Cells, Natural/immunology
• Lymphocyte Activation
• Pharmaceutical Preparations/analysis
• Pharmaceutical Preparations/metabolism
• Receptors, Fc/immunology

• cell differentiation
• human natural killer cells

• coronary artery disease
• cytokines
• inflammation
• leukocytes
• natural killer cell

Increasing evidences have pointed out the relevance of natural killer (NK) cells in organ-specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands up-regulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILCs), comprising the classical CD56⁺ NK cells, have a role in maintaining or alternating tissue homeostasis secreting protective and/or pro-inflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular-matrix components, and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

• DNAM1
• LAIR1
• NK cells
• NKG2D
• autoimmunity
• autoreactivity
• mesenchymal stromal cells
• regulatory NK cells

Natural killer (NK) cells are innate immune lymphocytes that function mainly as immune sentinels against viral infection and tumorigenesis. NK cell function is governed by inhibitory and activating signals arising from corresponding receptors. A prominent group of activating NK receptors is the natural cytotoxicity receptors (NCRs), which includes NKp30, NKp44, and NKp46. These receptors bind various diverse ligands of pathogenic, tumor, and even self origin. Type 1 diabetes mellitus (T1D) is a multifactorial autoimmune disease, in which insulin-producing beta (β) cells are ablated by the immune system. This killing of β cells is carried out mainly by T cells, but many other immune cells have been implicated in the pathogenesis of this disease. Importantly, NK cells were shown to be key participants in the initial autoimmune attack. It was shown that all β cells from humans and mice, healthy or sick, express an unknown ligand for the activating NKp46 receptor. In this review, we describe the role played by the NCRs in various pathologies with an emphasis on Type I diabetes.

• NCR
• NK cells
• NKp46
• beta cells
• diabetes