Fibroblast-like synoviocytes (FLSs) play a central role in RA pathogenesis and are the main cellular component in the inflamed synovium of patients with rheumatoid arthritis (RA). FLSs are emerging as promising new therapeutic targets in RA. However, fibroblasts perform many essential functions that are required for sustaining tissue homeostasis. Direct targeting of general fibroblast markers on FLSs is challenging because fibroblasts in other tissues might be altered and side effects such as reduced wound healing or fibrosis can occur. To date, no FLS-specific targeted therapies have been applied in the clinical management of RA. With the help of high-throughput technologies such as scRNA-seq in recent years, several specific pathogenic FLS subsets in RA have been identified. Understanding the characteristics of these pathogenic FLS clusters and the mechanisms that drive their differentiation can provide new insights into the development of novel FLS-targeting strategies for RA. Here, we discuss the pathogenic FLS subsets in RA that have been elucidated in recent years and potential strategies for targeting pathogenic FLSs.

中文翻译：

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靶向类风湿关节炎中的致病性成纤维细胞样滑膜细胞亚群


成纤维细胞样滑膜细胞 (FLS) 在 RA 发病机制中发挥核心作用，是类风湿性关节炎 (RA) 患者发炎滑膜的主要细胞成分。 FLS 正在成为 RA 有前景的新治疗靶点。然而，成纤维细胞执行维持组织稳态所需的许多基本功能。直接靶向 FLS 上的一般成纤维细胞标记具有挑战性，因为其他组织中的成纤维细胞可能会发生改变，并且可能会发生伤口愈合减少或纤维化等副作用。迄今为止，尚未将 FLS 特异性靶向治疗应用于 RA 的临床治疗。近年来，借助scRNA-seq等高通量技术，已经鉴定出RA中的几个特定致病性FLS亚群。了解这些致病性 FLS 簇的特征以及驱动其分化的机制可以为开发针对 RA 的新型 FLS 靶向策略提供新的见解。在这里，我们讨论近年来已阐明的 RA 致病性 FLS 亚群以及针对致病性 FLS 的潜在策略。