Rheumatoid arthritis is an immune-mediated inflammatory disease in which fibroblasts contribute to both joint damage and inflammation. Fibroblasts are a major cell constituent of the lining of the joint cavity called the synovial membrane. Under resting conditions, fibroblasts have an important role in maintaining joint homeostasis, producing extracellular matrix and joint lubricants. In contrast, during joint inflammation, fibroblasts contribute to disease pathology by producing pathogenic levels of inflammatory mediators that drive the recruitment and retention of inflammatory cells within the joint. Recent advances in single-cell profiling techniques have transformed our ability to examine fibroblast biology, leading to the identification of specific fibroblast subsets, defining a previously underappreciated heterogeneity of disease-associated fibroblast populations. These studies are challenging the previously held dogma that fibroblasts are homogeneous and are providing unique insights into their role in inflammatory joint pathology. In this review, we discuss the recent advances in our understanding of how fibroblast heterogeneity contributes to joint pathology in rheumatoid arthritis. Finally, we address how these insights could lead to the development of novel therapies that directly target selective populations of fibroblasts in the future.

中文翻译：

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炎症性关节病中的成纤维细胞病理学


类风湿性关节炎是一种免疫介导的炎症性疾病，其中成纤维细胞导致关节损伤和炎症。成纤维细胞是关节腔内壁（称为滑膜）的主要细胞成分。在静息条件下，成纤维细胞在维持关节稳态、产生细胞外基质和关节润滑剂方面发挥着重要作用。相反，在关节炎症期间，成纤维细胞通过产生致病水平的炎症介质来促进疾病病理，这些炎症介质驱动关节内炎症细胞的募集和保留。单细胞分析技术的最新进展改变了我们检查成纤维细胞生物学的能力，导致特定成纤维细胞亚群的鉴定，定义了先前未被充分认识的与疾病相关的成纤维细胞群体的异质性。这些研究挑战了以前认为成纤维细胞是同质的教条，并为它们在炎症关节病理学中的作用提供了独特的见解。在这篇综述中，我们讨论了我们对成纤维细胞异质性如何影响类风湿关节炎关节病理的最新进展。最后，我们讨论了这些见解如何导致未来直接针对选择性成纤维细胞群体的新疗法的开发。