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World J Diabetes. Apr 15, 2025; 16(4): 99936
Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.99936
T helper 17 cells and interleukin-17 immunity in type 1 diabetes: From pathophysiology to targeted immunotherapies
Georgi Vasilev, Maria Kokudeva, Elina Siliogka, Nathalia Padilla, Russka Shumnalieva, David Della-Morte, Camillo Ricordi, Antoaneta Mihova, Marco Infante, Tsvetelina Velikova
Georgi Vasilev, Clinic of Neurology and Department of Emergency Medicine, UMHAT "Sv. Georgi", Plovdiv 4000, Bulgaria
Georgi Vasilev, Russka Shumnalieva, Tsvetelina Velikova, Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
Maria Kokudeva, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia 1000, Bulgaria
Elina Siliogka, Faculty of Medicine, National and Kapodistrian University of Athens, Athens 11527, Attikí, Greece
Nathalia Padilla, Camillo Ricordi, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States
Russka Shumnalieva, Department of Rheumatology, Clinic of Rheumatology, University Hospital "St. Anna", Medical University-Sofia, Sofia 1612, Bulgaria
David Della-Morte, Department of Biomedicine and Prevention, Section of Clinical Nutrition and Nutrigenomics, University of Rome Tor Vergata, Rome 00133, Italy
Antoaneta Mihova, Department of Immunology, SMDL Ramus, Sofia 1527, Bulgaria
Marco Infante, Section of Diabetes & Metabolic Disorders, UniCamillus, Saint Camillus International University of Health Sciences, Rome 00131, Italy
Author contributions: Vasilev G, Velikova T and Infante M conceptualized the research article and wrote the manuscript; Vasilev G was the main contributor to the manuscript writing; Kokudeva M, Siliogka E, Padilla N, Shumnalieva R, Della-Morte D, Ricordi C and Mihova A wrote additional sections of the manuscript; Vasilev G, Kokudeva M and Siliogka E created the tables; Velikova T and Infante M created the figures; Infante M and Padilla N contributed to the critical revision of the manuscript; All authors approved the final version of the manuscript prior to its submission.
Supported by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, No. BG-RRP-2.004-0008.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Georgi Vasilev, MD, PhD, Assistant Professor, Clinic of Neurology and Department of Emergency Medicine, UMHAT "Sv. Georgi", Blvd. Peshtersko Shose 66, Plovdiv 4000, Bulgaria. vvasilev.georgi@gmail.com
Received: August 9, 2024
Revised: December 6, 2024
Accepted: February 7, 2025
Published online: April 15, 2025
Processing time: 207 Days and 13.4 Hours
Abstract

Type 1 diabetes (T1D) is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells, which ultimately results in insulinopenia, hyperglycemia and lifelong need for exogenous insulin therapy. In the pathophysiological landscape of T1D, T helper 17 cells (Th17 cells) and their hallmark cytokine, interleukin (IL)-17, play pivotal roles from disease onset to disease progression. In this narrative mini-review, we discuss the dynamic interplay between Th17 cells and IL-17 in the context of T1D, providing insights into the underlying immunologic mechanisms contributing to the IL-17-immunity-mediated pancreatic beta-cell destruction. Furthermore, we summarized the main animal and clinical studies that investigated Th17- and IL-17-targeted interventions as promising immunotherapies able to alter the natural history of T1D.

Keywords: Type 1 diabetes; T helper 17 cells; Interleukin-17; T helper 1 cells; Regulatory T cells; Anti-interleukin-17 treatment; Th17-targeted treatment

Core Tip: Recent research has identified Th17 cells and their primary effector cytokine, interleukin (IL)-17, as key players in the pathophysiology of type 1 diabetes (T1D). T helper 17 cells (Th17 cells) contribute to the autoimmune responses directed against pancreatic beta cells in T1D, promoting insulitis and beta-cell destruction. Understanding the role of Th17 cells and IL-17 in T1D pathophysiology offers new opportunities for targeted immunotherapies, which aim to modulate the altered immune responses and preserve residual beta-cell function in presymptomatic and new-onset T1D. Therefore, Th17 cell- and IL-17-targeted interventions may potentially represent future disease-modifying therapies able to improve clinical outcomes in patients with T1D at different stages of the disease.