Journal
SCIENCE
Volume 366, Issue 6464, Pages 494-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaw2719
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Funding
- Marie-Sklodowska Curie individual fellowship from the European Commission (H2020) [706353]
- Institut National de la Sante et de la Recherche Medicale
- Institut Curie
- Agence Nationale de la Recherche (ANR)
- Equipe Labellisee de la Ligue Contre le Cancer
- Marie Curie Actions (MSCA) [706353] Funding Source: Marie Curie Actions (MSCA)
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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 gamma t-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.
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