Role of the microbial metabolite-macrophage axis in tumor immunity

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07607
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: University of Shizuoka (2020-2021); Osaka University (2019)
• Principal Investigator: Umemoto Eiji 静岡県立大学, 薬学部, 教授 (90452440)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 粘膜免疫 / 代謝分子 / GPCR

Outline of Final Research Achievements

Gut microbial products pyruvate and lactic acid bind to G protein-coupled receptor GPR31 and induce dendrite protrusion of CX3CR1+ phagocyte in the small intestine. Here we found that GPR31 deficiency tends to promote tumorigenesis. Therefore, we analyzed regulatory T cells (Tregs) in the intestine. The number of Treg expressing RORgt+ in the small intestine was significantly reduced in GPR31-dificient mice. Oral administration of sodium pyruvate enhances oral tolerance in a GPR31-dependent manner. Thus, the pyruvate-GPR31 axis may play important roles in maintenance of gut homeostasis by inducing RORgt+ Tregs. The detailed role of the GPR31 signaling in tumor immunity needs to be addressed in further analyses.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、腸内細菌由来の代謝産物であるピルビン酸が、小腸貪食細胞上のG蛋白質共役型受容体GPR31に結合することで制御性T細胞サブセットを誘導し、経口免疫寛容を促進することが明らかになった。すなわち、ピルビン酸・乳酸―GPR31シグナルは腸管恒常性維持に重要な役割を果たすと考えられる。経口免疫寛容は食物アレルギーの成立に重要な役割持つことから、本研究の成果は将来的に食物アレルギーの予防や治療に応用できる可能性がある。