Gluten-Free Diet Induces Small-Scale Changes Across Multiple T-Cell Subsets in NOD Mice
Language English Country Germany Media print
Document type Journal Article
Grant support
68378050
Czech Academy of Sciences
22-21356S
Czech Science Foundation
LX22NPO5103
National Institute of Virology and Bacteriology funded by the European Union - Next Generation EU, Programme EXCELES
PubMed
40257397
PubMed Central
PMC12011074
DOI
10.1002/eji.202451559
Knihovny.cz E-resources
- Keywords
- NOD mice, T regulatory cells, gluten‐free diet, single‐cell transcriptomics, type I diabetes,
- MeSH
- Lymphocyte Activation immunology MeSH
- Diet, Gluten-Free * MeSH
- Cell Differentiation MeSH
- Diabetes Mellitus, Type 1 * immunology MeSH
- Mice, Inbred NOD MeSH
- Mice MeSH
- T-Lymphocyte Subsets * immunology MeSH
- Transcriptome MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Nonobese diabetic (NOD) mice are a widely used animal model to study mechanisms leading to autoimmune diabetes. A gluten-free diet reduces and delays the incidence of diabetes in NOD mice, but the underlying mechanisms remain largely unknown. In this study, we performed single-cell transcriptomic and flow cytometry analysis of T cells and innate lymphocytes in the spleen and pancreatic lymph nodes of NOD mice fed a gluten-free or standard diet. We observed that the gluten-free diet did not induce a substantial alteration in the abundance or phenotype of any lymphocyte subset that would directly explain its protective effect against diabetes. However, the gluten-free diet induced subtle changes in the differentiation of subsets with previously proposed protective roles in diabetes development, such as Tregs, activated γδT cells, and NKT cells. Globally, the gluten-free diet paradoxically promoted activation and effector differentiation across multiple subpopulations and induced genes regulated by IL-2, IL-7, and IL-15. In contrast, the standard diet induced type I interferon-responsive genes. Overall, the gluten-free diet might prevent diabetes in NOD mice by inducing small-scale changes in multiple cell types rather than acting on a specific lymphocyte subset.
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