2. Academic Validation
  3. Sulfated bile acid is a host-derived ligand for MAIT cells

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

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.

Figures
Products