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REVIEW article

Front. Immunol.

Sec. T Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1664255

This article is part of the Research TopicEpigenetic Regulation of T Cell Function in Type 1 DiabetesView all 3 articles

Linking Epigenetic Mechanisms of T Cell Dysfunction with Pathophysiology of Type 1 Diabetes Mellitus

Provisionally accepted
Abdullah JabriAbdullah Jabri1Abdulrahman ElsaltiAbdulrahman Elsalti2Mohamed AlsharifMohamed Alsharif3Raghad AlsharifRaghad Alsharif3Tasnim AbbadTasnim Abbad3Dania AlsibaiDania Alsibai3Bader TaftafaBader Taftafa3Abdulaziz MhannayehAbdulaziz Mhannayeh3Mohammad Imran KhanMohammad Imran Khan4Ahmed YaqinuddinAhmed Yaqinuddin5*
  • 1College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  • 2Istanbul Medipol Universitesi, Fatih, Türkiye
  • 3Alfaisal University College of Medicine, Riyadh, Saudi Arabia
  • 4King Faisal Specialist Hospital & Research Centre - Jeddah, Jeddah, Saudi Arabia
  • 5Alfaisal University, Riyadh, Saudi Arabia

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β-cell destruction by autoreactive T cells is a hey hallmark of type 1 diabetes mellitus (T1D). Epigenetic mechanisms—including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs—play critical roles in regulating T-cell development, activation, and tolerance. Disruption of these processes contributes to immune imbalance and the onset of T1D. This review summarizes current insights into how epigenetic regulation shapes T-cell function and highlights emerging evidence linking these changes to environmental influences such as gut microbiota, diet, and viral infections. Exploring the interaction between genetic susceptibility and environmental triggers through an epigenetic framework not only advances our understanding of T1D pathogenesis but also provides opportunities for biomarker discovery and the development of targeted epigenetic therapies. With further research, these advances hold promise for improving precision medicine strategies in T1D.

Keywords: type 1 diabetes, epigenetics, T-cell dysfunction, Autoimmunity, DNA methyaltion

Received: 11 Jul 2025; Accepted: 15 Oct 2025.

Copyright: © 2025 Jabri, Elsalti, Alsharif, Alsharif, Abbad, Alsibai, Taftafa, Mhannayeh, Khan and Yaqinuddin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ahmed Yaqinuddin, ayaqinuddin@alfaisal.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material