MAIT cells are imprinted by the microbiota in early life and promote tissue repair

Science. 2019 Oct 25;366(6464):eaax6624. doi: 10.1126/science.aax6624.


How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / metabolism
  • Germ-Free Life
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Interleukin-1 / immunology
  • Interleukin-17 / immunology
  • Interleukin-18 / immunology
  • Interleukin-23 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota / immunology*
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology
  • Mucosal-Associated Invariant T Cells / cytology*
  • Riboflavin / biosynthesis*
  • Skin / immunology
  • Skin / microbiology
  • Specific Pathogen-Free Organisms
  • Wound Healing / immunology*


  • Histocompatibility Antigens Class I
  • IL17A protein, human
  • IL18 protein, human
  • Interleukin-1
  • Interleukin-17
  • Interleukin-18
  • Interleukin-23
  • Minor Histocompatibility Antigens
  • Mr1 protein, mouse
  • Riboflavin