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Bacterial metabolites, e.g. pyruvate and lactate, induce a dendrite extension of CX3CR1high myeloid cells into the intestinal lumen via GPR31. However, it remains unclear whether the pyruvate\u2013GPR31 axis is involved in the induction of oral tolerance. Here, we show that pyruvate enhances oral tolerance in a GPR31-dependent manner. In ovalbumin (OVA)-fed Gpr31-deficient mice, an OVA-induced delayed-type hypersensitivity response was substantially induced, demonstrating the defective induction of oral tolerance in Gpr31-deficient mice. The percentage of ROR\u03b3t+ Treg cells in the small intestine was reduced in Gpr31-deficient mice. In pyruvate-treated wild-type mice, a low dose of OVA efficiently induced oral tolerance. IL-10 production from intestinal CX3CR1high myeloid cells was increased by OVA ingestion in wild-type mice, but not in Gpr31-deficient mice. CX3CR1high myeloid cell-specific IL-10-deficient mice showed a defective induction of oral tolerance to OVA and a decreased accumulation of OVA-specific Treg cells in the small intestine. These findings demonstrate that pyruvate enhances oral tolerance through a GPR31-dependent effect on intestinal CX3CR1high myeloid cells.<\/jats:p>","DOI":"10.1093\/intimm\/dxac010","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T12:34:43Z","timestamp":1647520483000},"page":"343-352","source":"Crossref","is-referenced-by-count":18,"title":["Pyruvate enhances oral tolerance via GPR31"],"prefix":"10.1093","volume":"34","author":[{"given":"Qizhi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka, 565-0871 , Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Umemoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka, 565-0871 , Japan"},{"name":"Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka , Shizuoka 422-8526 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka, 565-0871 , Japan"},{"name":"Institute for Quantitative Biosciences, University of Tokyo , Bunkyo-ku, Tokyo 113-0032 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisako","family":"Kayama","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka, 565-0871 , Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 , Japan"},{"name":"Institute for Advanced Co-Creation Studies, Osaka University , Suita, Osaka 565-0871 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Baba","sequence":"additional","affiliation":[{"name":"Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 , Japan"},{"name":"Center for Infectious Disease Education and Research, Osaka University , Suita, Osaka 565-0871 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryu","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka, 565-0871 , Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 , Japan"},{"name":"Institute for Open and Transdisciplinary Research Initiative, Osaka University , Suita, Osaka 565-0871 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita, Osaka, 565-0871 , Japan"},{"name":"WPI Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 , Japan"},{"name":"Center for Infectious Disease Education and Research, Osaka University , Suita, Osaka 565-0871 , Japan"},{"name":"Institute for Open and Transdisciplinary Research Initiative, Osaka University , Suita, Osaka 565-0871 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"2022070402562247600_CIT0001","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-065X.2011.01017.x","article-title":"Oral tolerance","volume":"241","author":"Weiner","year":"2011","journal-title":"Immunol. 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