Sulfated bile acid is a host-derived ligand for MAIT cells.

Autor: Ito E; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan., Inuki S; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Kyoto 606-8501, Japan., Izumi Y; Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan., Takahashi M; Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan., Dambayashi Y; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Kyoto 606-8501, Japan., Ciacchi L; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Awad W; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Takeyama A; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan., Shibata K; Department of Microbiology and Immunology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8505, Japan., Mori S; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan., Mak JYW; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia., Fairlie DP; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia., Bamba T; Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan., Ishikawa E; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan., Nagae M; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan., Rossjohn J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.; Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK., Yamasaki S; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.; Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka, 565-0871, Japan.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Jan 26; Vol. 9 (91), pp. eade6924. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1126/sciimmunol.ade6924
Abstrakt: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize bacterial riboflavin-based metabolites as activating antigens. Although MAIT cells are found in tissues, it is unknown whether any host tissue-derived antigens exist. Here, we report that a sulfated bile acid, cholic acid 7-sulfate (CA7S), binds the nonclassical MHC class I protein MR1 and is recognized by MAIT cells. CA7S is a host-derived metabolite whose levels were reduced by more than 98% in germ-free mice. Deletion of the sulfotransferase 2a family of enzymes ( Sult2a1-8 ) responsible for CA7S synthesis reduced the number of thymic MAIT cells in mice. Moreover, recognition of CA7S induced MAIT cell survival and the expression of a homeostatic gene signature. By contrast, recognition of a previously described foreign antigen, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), drove MAIT cell proliferation and the expression of inflammatory genes. Thus, CA7S is an endogenous antigen for MAIT cells, which promotes their development and function.
Databáze: MEDLINE