Science 366, eaax6624 (2019)

Host interactions with commensal microbes at barrier tissues serve a crucial role in sculpting immune system responsiveness and in engendering tolerogenic networks. In Science, Constantinides et al. investigate how commensals influence the establishment of mucosal-associated invariant T cells (MAIT cells) in the skin of neonatal mice and how these interactions dictate adult immune responses to cutaneous infection. Surprising variability in the frequency of MAIT cells exists among separately housed mice, but not among their cage mates. MAIT cells must be established by 2–3 weeks of age, and their frequency, which remains fixed throughout life, is dictated by the abundance of riboflavin-producing microbiota during this early time period. Skin MAIT cells become exclusively cytokine IL-17A–producing cells and exhibit a transcriptional program distinct from that of other tissue-resident MAIT cells. After skin infection, MAIT cells respond to local signaling by IL-1 and IL-18, in conjunction with riboflavin-MR1-dependent antigen presentation, and secrete IL-17A and thereby promote wound healing.