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

• DOI: 10.1126/science.aaw2719
• Publication Date: 2019-08-29T22:54:05Z
• Authors: François Legoux; Déborah Bellet; Celine Daviaud; Yara El Morr; Aurelie Darbois; Kristina Niort; Emanuele Procopio; Marion Salou; Jules Gilet; Bernhard Ryffel; Aurélie Balvay; Anne Foussier; Manal Sarkis; Ahmed El Marjou; Frederic Schmidt; Sylvie Rabot; Olivier Lantz
• Keywords: 570; [SDV]Life Sciences [q-bio]; Receptors, Antigen, T-Cell; 610; Mucosal-Associated Invariant T Cells; Minor Histocompatibility Antigens; Mice; 03 medical and health sciences; Escherichia coli; [CHIM]Chemical Sciences; Animals; Germ-Free Life; Symbiosis; Lung; Ribitol; Mice, Knockout; 0303 health sciences; Mucous Membrane; Escherichia coli Proteins; Histocompatibility Antigens Class I; Gastrointestinal Microbiome; Specific Pathogen-Free Organisms; 3. Good health; Mice, Inbred C57BL; Nucleotide Deaminases; Spleen; Sugar Alcohol Dehydrogenases

Commensals rule the MAITrix

Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT cells recognize microbial small molecules presented by the major histocompatibility complex class Ib molecule MR1. MAIT cells are absent in germ-free mice, and the mechanisms by which microbiota control MAIT cell development are unknown (see the Perspective by Oh and Unutmaz). Legoux et al. show that, in mice, development of MAIT cells within the thymus is governed by the bacterial product 5-(2-oxopropylideneamino)-6- d -ribitylaminouracil, which rapidly traffics from the mucosa to the thymus, where it is captured by MR1 and presented to developing MAIT cells. Constantinides et al. report that MAIT cell induction only occurs during a limited, early-life window and requires exposure to defined microbes that produce riboflavin derivatives. Continual interactions between MAIT cells and commensals in the skin modulates tissue repair functions. Together, these papers highlight how the microbiota can direct immune cell development and subsequent function at mucosal sites by secreting compounds that act like self-antigens.

Science , this issue p. 494 , p. eaax6624 ; see also p. 419