Pyruvate enhances oral tolerance via GPR31

Qizhi Liu, Eiji Umemoto, Naoki Morita, Hisako Kayama, Yoshihiro Baba, Tomohiro Kurosaki, Ryu Okumura, Kiyoshi Takeda

Research output: Contribution to journalArticlepeer-review

Abstract

CX3CR1high myeloid cells in the small intestine mediate the induction of oral tolerance by driving regulatory T (Treg) cells. 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-GPR31 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 RORγt+ 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.

Original languageEnglish
Pages (from-to)343-352
Number of pages10
JournalInternational immunology
Volume34
Issue number7
DOIs
Publication statusPublished - Jul 1 2022

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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