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.

• Klíčová slova
• NOD mice, T regulatory cells, gluten‐free diet, single‐cell transcriptomics, type I diabetes,
• MeSH
• aktivace lymfocytů imunologie   MeSH
• bezlepková dieta * MeSH
• buněčná diferenciace MeSH
• diabetes mellitus 1. typu * imunologie   MeSH
• myši inbrední NOD MeSH
• myši MeSH
• T-lymfocyty - podskupiny * imunologie   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Invariant natural killer T (iNKT) cells are CD1d-restricted T cells with regulatory functions. iNKT cells are numerically and functionally deficient in experimental models of type 1 diabetes mellitus (T1DM). Moreover, various experimental strategies correcting the defect of or stimulating iNKT cells prevent T1DM. Here, we review the data on the role of iNKT cells in the development of T1DM and discuss indications, obstacles and prospects of the use of iNKT cell manipulations in the prevention and treatment of human T1DM.

• MeSH
• diabetes mellitus 1. typu imunologie   prevence a kontrola   terapie   MeSH
• lidé MeSH
• NKT buňky imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH