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

  • Sci Immunol. 2024 Jan 26;9(91):eade6924. doi: 10.1126/sciimmunol.ade6924.
Emi Ito  1  2 ,  Shinsuke Inuki  3 ,  Yoshihiro Izumi  4 ,  Masatomo Takahashi  4 ,  Yuki Dambayashi  3 ,  Lisa Ciacchi  5 ,  Wael Awad  5 ,  Ami Takeyama  1  2 ,  Kensuke Shibata  6 ,  Shotaro Mori  1  2 ,  Jeffrey Y W Mak  7 ,  David P Fairlie  7 ,  Takeshi Bamba  4 ,  Eri Ishikawa  1  2 ,  Masamichi Nagae  1  2 ,  Jamie Rossjohn  5  8 ,  Sho Yamasaki  1  2  9
Affiliations
  • 1. Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
  • 2. Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
  • 3. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Kyoto 606-8501, Japan.
  • 4. Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
  • 5. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • 6. Department of Microbiology and Immunology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755-8505, Japan.
  • 7. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
  • 8. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
  • 9. Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka, 565-0871, Japan.
PMID: 38277465 DOI: 10.1126/sciimmunol.ade6924
Abstract

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.

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