Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China.
Department of Joint Surgery, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Nat Commun. 2024 Jan 2;15(1):113. doi: 10.1038/s41467-023-44304-w.
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.
肥大细胞表型和功能具有异质性，其状态可能受局部微环境控制。因此，需要进行特定分析以了解肥大细胞在特定疾病中是作为强大的参与者还是可有可无的旁观者发挥作用。在这里，我们表明，类风湿关节炎（RA）患者炎症性滑膜组织中的肥大细胞脱颗粒是通过 MAS 相关 G 蛋白偶联受体 X2（MRGPRX2）诱导的，并且肥大细胞上 MHC Ⅱ类和共刺激分子的表达上调。用抗白细胞介素 17A 和肥大细胞膜稳定剂 cromolyn 钠联合治疗胶原诱导性关节炎小鼠，可显著降低临床严重程度和骨侵蚀。本研究结果表明，受滑膜微环境影响的肥大细胞有助于疾病进展，可能为 RA 提供进一步的肥大细胞靶向治疗。
