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
  • 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: [email protected].
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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