Journal Article

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

Niort, Kristina, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM) ; Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Foussier, Anne, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Legoux, François, Daviaud, Celine, ANR-16-CE15-0020,MAIT,Biologie des cellules MAIT in vivo en situation normale ou pathologique, El Marjou, Ahmed, Rabot, Sylvie, Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143) ; Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université d

2019

Overview

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 the development of mucosally targeted T cells in a process blurring the distinction between exogenous antigens and self-antigens.

• Publisher: American Association for the Advancement of Science (AAAS),CCSD,American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Antigens / Autoantigens / Bacteria / Chemical Sciences / Commensals / Escherichia coli / Escherichia coli Proteins / Gastrointestinal Microbiome / Germ-Free Life / Germfree / Histocompatibility Antigens Class I - immunology / Homeostasis / Immune system / Invariants / Life Sciences / Lung - cytology / Lymphocytes / Lymphocytes T / Major histocompatibility complex / Metabolites / Mice / Mice, Inbred C57BL / Mice, Knockout / Microbiota / Microorganisms / Minor Histocompatibility Antigens - immunology / Mucosa / Mucosal-Associated Invariant T Cells - cytology / Mucous Membrane - immunology / Nucleotide Deaminases / Receptors, Antigen, T-Cell - immunology / Ribitol - analogs & derivatives / Ribitol - immunology / Riboflavin / Skin / Specific Pathogen-Free Organisms / Spleen - cytology / Sugar Alcohol Dehydrogenases / Symbiosis / Thymus / Thymus Gland - cytology / Uracil - analogs & derivatives / Uracil - immunology
• ISBN: 0004931779000