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Science. 2019 Aug 29. pii: eaaw2719. doi: 10.1126/science.aaw2719. [Epub ahead of print]

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

Author information

1
INSERM U932, PSL University, Institut Curie, Paris 75005, France. olivier.lantz@curie.fr francois.legoux@curie.fr.
2
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas 78350, France.
3
INSERM U932, PSL University, Institut Curie, Paris 75005, France.
4
Animal Facility, Institut Curie, Paris 75005, France.
5
Recombinant Protein Facility, Institut Curie, Paris 75005, France.
6
CNRS UMR7355, Université d'Orléans, Orléans 45067, France.
7
CNRS UMR3666, INSERM U1143, PSL University, Institut Curie, Paris 75005, France.
8
Laboratoire d'Immunologie Clinique, Institut Curie, Paris 75005, France.
9
Centre d'Investigation Clinique en Biothérapie Gustave-Roussy Institut Curie (CIC-BT1428), Institut Curie, Paris 75005, France.

Abstract

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 γt-positive MAIT cells. Thus, a microbiota-derived metabolite controls development of mucosally targeted T cells, in a process blurring the distinction between exogenous and self-antigens.

PMID:
31467190
DOI:
10.1126/science.aaw2719

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