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Microbial metabolites control the thymic development of mucosal-associated invariant T cells

By François Legoux, Déborah Bellet, Celine Daviaud, Yara El Morr, Aurélie Darbois, Kristina Niort, Emanuele Procopio, Marion Salou, Jules Gilet, Bernhard Ryffel, Aurélie Balvay, Anne Foussier, Manal Sarkis, Ahmed El Marjou, Frédéric SCHMIDT, Sylvie Rabot and Olivier Lantz

Abstract

International audienceHow 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 γt-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

Topics: [CHIM]Chemical Sciences, [SDV]Life Sciences [q-bio]
Publisher: 'American Association for the Advancement of Science (AAAS)'
Year: 2019
DOI identifier: 10.1126/science.aaw2719
OAI identifier: oai:HAL:hal-02349402v1
Provided by: HAL Descartes
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