We wish to determine the role of innate-like T cells in the regulation of Type 1 diabetes (T1D). Natural killer T (NKT) cells and Mucosal Associated Invariant T (MAIT) cells are non-conventional T cells that recognized lipid antigens and vitamin metabolites, respectively. As such they play a critical role as sensors of metabolic abnormalities. Importantly these innate-like T cells can regulate both innate and adaptive immunity. MAIT cells are present in various tissues and more particularly in the liver and the gut, where they are activated by bacterial ligands. Due to the impact of microbiota in the development of T1D, we are presently analyzing the role of MAIT cells in this pathology. The studies are performed in patients as well as in mouse models. In T1D patients, circulating MAIT cells are significantly decreased, and their activation status is more pronounced in young children. We have generated non-obese diabetic (NOD) mice devoid of MAIT cells (MR1-/-), as well as transgenic NOD mice exhibiting high MAIT cell frequency. Our data in murine models revealed a protective role of MAIT cells against the development of T1D. MAIT cells play a pivotal role in the maintenance of the gut integrity thereby dampening the autoimmune response. In parallel to the murine studies, we are analyzing MAIT cells in different cohorts of T1D patients.
Keywords
MAIT cells, Intestinal Microbiota, Immunology, Type 1 Diabetes