GSE128814
Early-life microbial exposure imprints the abundance of mucosal-associated invariant T cells and subsequent interactions modulate their function
How early exposure to the microbiota impacts long-term host immunity remains poorly understood. Here we show that the development of mucosal-associated invariant T (MAIT) cells depends on early-life exposure to microbes that synthesize riboflavin, such as Enterobacteriaceae. This microbial imprinting relies on a specific temporal window, after which MAIT cell development is permanently impaired. In adults, MAIT cells are a dominant population of IL-17A-producing lymphocytes within the skin that can subsequently respond to skin commensals in an IL-1 and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing and limits skin inflammation. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells that sequentially controls both tissue-imprinting and subsequent response to injury and inflammation. Overall design: Examination of CD4+CD25- T cells and MAIT T cells from skin of control  or S. epidermidis LM061-exposed mice. Examination of MAIT cells from different tissues.