How the microbiota modulate immune functions remains poorly understood. Mucosal-associated invariant T (MAIT) cells are implicated in mucosal homeostasis and absent in germ-free mice. Here, we show that commensal bacteria govern murine MAIT intrathymic development, as MAIT cells did not recirculate to the thymus. MAIT development required RibD expression in bacteria, indicating that production of the MAIT antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) was necessary. 5-OP-RU rapidly traveled from mucosal surfaces to the thymus, where it was captured by the major histocompatibility complex class Ib molecule MR1. This led to increased numbers of the earliest MAIT precursors and the expansion of more mature receptor-related, orphan receptor γt–positive MAIT cells. Thus, a microbiota-derived metabolite controls the development of mucosally targeted T cells in a process blurring the distinction between exogenous antigens and self-antigens.

Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic-beta cells by the immune system involving innate and adaptive immune cells. Mucosal-associated invariant T (MAIT) cells are innate-like T-cells recognizing bacterial riboflavin-precursor derivatives presented by the MHC-I related molecule, MR1. Since T1D is associated with gut microbiota modification, we investigated MAIT cells in this pathology. In T1D patients and non-obese diabetic mice, we detected MAIT cell alterations, including increased granzyme B production, which occur before disease onset. Analysis of NOD mice deficient for MR1 and therefore lacking MAIT cells revealed a loss of gut integrity, increased anti-islet responses associated with exacerbated diabetes. Altogether our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. MAIT cell monitoring could represent a new biomarker in T1D while their manipulation may open new therapeutic strategies.