Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive joint disease. To date, the etiology and pathogenesis of RA have not been fully elucidated, but a large number of studies have indicated that hypoxia is an important feature of RA. Our study was designed to probe how hypoxia-induced exosome (exo) derived from synovial fibroblasts (SFs) affect RA. In this study, we found that hypoxic environment existed in synovial tissue of RA, and miR-424 expression was increased in RA, and exosome derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation, which Th17 cells increased and Treg cells decreased. Besides, SFs-exo affected the expression of related inflammatory cytokines. And, we also found that FOXP3 was a target gene of miR-424 and exo-miR-424 KD inhibited RA worsening. These results suggested that SFs-exo in hypoxia aggravates rheumatoid arthritis by regulating Treg/Th17 balance and thus may be a potential therapeutic target for RA.

Impact statement

A comparative study of osteoarthritis (OA) and RA mice was implemented to suggest that miR-424 expression was increased in RA, and exosome-miR-424 derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation in which Th17 cells increased and Treg cells decreased via targeting FOXP3. And thus, miR-424 may be a potential therapeutic target for RA.

中文翻译：

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缺氧条件下来自滑膜成纤维细胞的外泌体通过调节 Treg/Th17 平衡加重类风湿性关节炎。

类风湿性关节炎（RA）是一种以慢性破坏性关节疾病为特征的全身性自身免疫性疾病。迄今为止，RA的病因和发病机制尚未完全阐明，但大量研究表明缺氧是RA的一个重要特征。我们的研究旨在探讨源自滑膜成纤维细胞 (SF) 的缺氧诱导的外泌体 (exo) 如何影响 RA。本研究发现RA滑膜组织存在缺氧环境，RA中miR-424表达增加，滑膜成纤维细胞来源的外泌体（SFs-exo）可显着诱导T细胞分化，其中Th17细胞增加，Treg增加。细胞减少。此外，SFs-exo 影响相关炎性细胞因子的表达。而且，我们还发现 FOXP3 是 miR-424 的靶基因，exo-miR-424 KD 抑制 RA 恶化。

影响陈述

对骨关节炎 (OA) 和 RA 小鼠进行的比较研究表明，RA 中 miR-424 表达增加，来自滑膜成纤维细胞 (SFs-exo) 的外泌体-miR-424 可显着诱导 T 细胞分化，其中 Th17 细胞通过靶向 FOXP3 增加和减少 Treg 细胞。因此，miR-424 可能是 RA 的潜在治疗靶点。