François LEGOUX

Metabolite-specific T cells: original development controlled by the microbiota

Abstract:  

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that play an important role in mucosal homeostasis. MAIT cells recognize vitamin B2 metabolites produced by bacteria and presented by the MHC molecule MR1. MAIT cells are absent in germ-free mice, though the mechanisms by which the microbiota controls MAIT cell development are unknown. Using single-cell RNAseq and Gene Regulatory Network (GRN) analysis, we defined the sequence of transcription factors controlling MAIT cell development. We identified a number of genes involved in cell proliferation, and we report that MAIT cell proliferation is impaired in germ-free mice. Intrathymic development of MAIT cells was governed by the bacterial product 5-OP-RU. 5-OP-RU rapidly travelled from the mucosa to the thymus, where it was captured by MR1 and presented to developing MAIT cells. Thus, the microbiota is able to direct immune cell development from distant locations by producing a compound that acts like a self-antigen.

François LEGOUX INSTITUT CURIE

Invited by Reynald GILLET

>> Thursday 26 September 2019 at 11:00 - IGDR conference room, ground floor, building 4 / Villejean Campus

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