ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
IL17-deficient NOD mice are protected from autoimmune diabetes due to decreased antigen presentation and T cell activation
Provisionally accepted
- 1Cardiff University Cardiff Division of Infection and Immunity, Cardiff, United Kingdom
- 2Yale School of Medicine Department of Internal Medicine, New Haven, United States
- 3Sir Run Run Hospital Nanjing Medical University, Nanjing, China
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IL-17 is a key cytokine helping preserve the intestinal barrier against infections; however, the T cells that primarily secrete IL-17 (Th17) can promote the development of autoimmunity. In Type 1 diabetes, the role of IL-17 is less well understood, with many studies evaluating the role of IL-17, without considering changes within the intestine. Furthermore, therapeutically targeting IL-12/IL-23 (upstream of IL-17) or IL-17 directly can help preserve insulin-producing beta cells in those newly diagnosed with Type 1 diabetes. Thus, there is a need to better understand how IL-17 may modulate susceptibility to Type 1 diabetes by linking intestinal changes to type 1 diabetes development. To do this, we studied IL-17-deficient NOD mice to understand the role of IL-17 in mediating susceptibility to Type 1 diabetes in vivo and in vitro. Our study showed that IL-17-deficient NOD mice were protected from autoimmune diabetes, and in vivo adoptive transfer studies showed that both immune and non-immune cells are important for modulating diabetes development. We found significant reductions in both regulatory T cells and inflammatory T-bet-expressing CD8+ T cells, while Type 3 Innate Lymphoid Cells (ILC3s) were expanded. These changes were found to be mediated through altered gut microbiota composition of the IL-17-deficient NOD mice. Finally, we demonstrated that intestinal epithelial cells from IL-17-deficient NOD mice were less able to present autoantigen to autoreactive CD8+ T cells, with reduced proinflammatory cytokine secretion. This effect was specific to IL-17 deficiency, as addition of exogenous IL-17 resulted in improved antigen presentation to autoreactive CD8+ T cells. Together, our data suggest a novel role for IL-17 in modulating epithelial cell function and antigen presentation within the intestinal tissue, resulting in reduced autoantigen-specific T cell responses and enhanced protection from autoimmune diabetes. Better understanding of how targeted IL-17 blockade could be administered to the intestine may help better prevent the development of Type 1 diabetes.
Keywords: Gut Microbiota, IL17, ILC, T cell, type 1 diabetes
Received: 19 Oct 2025; Accepted: 17 Dec 2025.
Copyright: © 2025 Pearson, Li, Huang, Peng, Wong and Wen. 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:
James Alexander Pearson
Li Wen
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