Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis

Yunxuan Lei, Xin Guo, Yanping Luo, Xiaoyin Niu, Yebin Xi, Lianbo Xiao, Dongyi He, Yanqin Bian, Yong Zhang, Li Wang, Xiaochun Peng (), Zhaojun Wang () and Guangjie Chen ()
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Yunxuan Lei: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Xin Guo: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Yanping Luo: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Xiaoyin Niu: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Yebin Xi: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Lianbo Xiao: Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Dongyi He: Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine
Yanqin Bian: Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine
Yong Zhang: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Li Wang: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Xiaochun Peng: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Zhaojun Wang: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology
Guangjie Chen: Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

Date: 2024
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DOI: 10.1038/s41467-023-44304-w

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