American Association of Immunologists, The Journal of Immunology, 1_Supplement(204), p. 84.2-84.2, 2020
DOI: 10.4049/jimmunol.204.supp.84.2
American Association for the Advancement of Science, Science, 6464(366), 2019
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Abstract Early-life microbial colonization has been shown to impart long-lasting effects on host fitness. Because mucosal-associated invariant T (MAIT) cells are predominantly located in tissues colonized by the microbiota and characterized by their recognition of microbial-derived riboflavin intermediates, they are thought to be particularly dependent on the microbiota. However, little is known about their development and how they contribute to tissue physiology. MAIT cells accumulated in barrier tissues between 2 and 3 weeks of age, suggesting that MAIT cells develop during a very specific temporal window and in response to defined microbial exposure. The isolation of early-life intestinal commensals and subsequent colonization of neonatal germ-free mice with defined bacteria induced MAIT cell development. Conversely, colonization later in life failed to promote their development within tissues, indicating that microbial exposure must occur during an early-life window. Following their development, MAIT cells represented a dominant type-17 subset in the skin and cutaneous MAIT cells uniquely expressed a transcriptional program associated with tissue repair. Cutaneous MAIT cells responded locally to skin commensals in a manner that required IL-1 and IL-18, as well as MR1-mediated presentation of riboflavin metabolites. Topical application of a riboflavin derivative selectively increased MAIT cells in the skin and was sufficient to promote cutaneous wound healing. Our work demonstrates that MAIT cells are induced during a specific early-life window in response to riboflavin-synthesizing commensals, which permanently imprints the abundance of this subset in tissues, thereby controlling tissue repair and homeostasis.