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  3. Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients

Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients

  • Cell Rep. 2024 Oct 22;43(10):114858. doi: 10.1016/j.celrep.2024.114858.
Anqi Li 1,  Xiaoyi Wang 2,  Jingwen Li 1,  Xiaoyu Li 1,  Jue Wang 1,  Yang Liu 2,  Zhihong Wang 3,  Xiaobing Yang 4,  Jiapeng Gao 5,  Juanjie Wu 2,  Tao Sun 3,  Lixia Huo 2,  Yanfeng Yi 6,  Jiantong Shen 1,  Jiexun Cai 1,  Yunliang Yao 7
Affiliations

Affiliations

  • 1 School of Medicine & Nursing, Huzhou University, Huzhou, China.
  • 2 First Affiliated Hospital, Huzhou University, Huzhou, China.
  • 3 Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, China.
  • 4 Third Affiliated Hospital, Huzhou University, Huzhou, China.
  • 5 Institute of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • 6 School of Life and Health Sciences, Huzhou College, Huzhou, China.
  • 7 School of Medicine & Nursing, Huzhou University, Huzhou, China; First Affiliated Hospital, Huzhou University, Huzhou, China. Electronic address: yaoyunliang@zjhu.edu.cn.
PMID: 39392754 DOI: 10.1016/j.celrep.2024.114858
Abstract

Rheumatoid arthritis (RA) is marked by joint damage and inflammation, with B cells playing a key role by generating autoantibodies. This study shows that G protein-coupled receptor 40 (GPR40) deficiency in B cells leads to increased activation, proliferation, antibody production, germinal center formation, and class switch recombination. GPR40 regulates Plcγ2 phosphorylation and intracellular calcium flux downstream of the B cell receptor by binding to the Gαq protein. In GPR40-deficient mice, susceptibility to collagen-induced arthritis was higher. GPR40 agonists showed potential as therapeutic agents, and their reduced expression in patients with RA correlated with disease onset, suggesting GPR40 as a potential therapeutic target and diagnostic marker.

Keywords

B cell; CP: Immunology; GPR40; collagen-induced arthritis; rheumatoid arthritis.

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