CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis
CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis
复制标题
CD109 调节炎症反应，是类风湿性关节炎发病机制所必需的
DOI：
10.1136/annrheumdis-2019-215473
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发表时间：
2019-12-01
影响因子：
27.4
通讯作者：
Han, Jinxiang
中科院分区：
文献类型：
--
作者：
Song, Guanhua;Feng, Tingting;Han, Jinxiang
目的探讨CD 109在类风湿关节炎（RA）成纤维样滑膜细胞（FLS）中的作用及其作为治疗靶点的可能性。方法检测类风湿关节炎（RA）患者和胶原诱导性关节炎（CIA）模型小鼠滑膜组织和滑膜液中CD 109的表达。开发CD 109缺陷型小鼠以评估CIA的严重性。设计了小干扰RNA和抗CD 109中和抗体（抗CD 109），用于RA FLS和CIA的功能或治疗研究。结果CD 109在RA患者和CIA小鼠的滑膜组织中均有高表达。RA FLS中CD 109的表达被炎症刺激物如白细胞介素-1 β和肿瘤坏死因子-α上调。沉默CD 109或抗CD 109治疗可减少促炎因子产生、细胞迁移、侵袭、化学吸引潜力和破骨细胞分化，从而减少体外RA FLS的有害炎症反应。在CIA模型中，缺乏CD 109的小鼠免受关节炎的影响。抗CD 109治疗预防了CIA病变的发作并改善了CIA病变的严重程度。结论CD 109具有抗关节炎的作用，抑制CD 109可能成为治疗RA的新策略。
Objective The aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target. Methods CD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA. Results CD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1β and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions. Conclusion Our study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.