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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靶向类风湿性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 发病机制中起着核心作用，并且是类风湿性关节炎 （RA） 患者发炎滑膜中的主要细胞成分。FLS 正在成为 RA 中很有前途的新治疗靶点。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志物具有挑战性，因为其他组织中的成纤维细胞可能会发生变化，并且可能会出现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 的临床管理。近年来，在 scRNA-seq 等高通量技术的帮助下，已经鉴定出 RA 中的几种特异性致病性 FLS 亚群。了解这些致病性 FLS 簇的特征和驱动其分化的机制可以为开发新的 RA 靶向 FLS 策略提供新的见解。在这里，我们讨论了近年来阐明的 RA 中的致病性 FLS 亚群以及靶向致病性 FLS 的潜在策略。