Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), Queen Elizabeth Hospital, University of Birmingham, Birmingham, UK.
Immunol Rev. 2021 Jul;302(1):163-183. doi: 10.1111/imr.12986. Epub 2021 Jun 6.
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.
类风湿关节炎是一种免疫介导的炎症性疾病，其中成纤维细胞既参与关节损伤，也参与炎症反应。成纤维细胞是关节腔衬里（称为滑膜）的主要细胞成分。在静息状态下，成纤维细胞在维持关节内环境稳定方面发挥着重要作用，产生细胞外基质和关节润滑剂。相比之下，在关节炎症期间，成纤维细胞通过产生促炎介质的病理水平来促进疾病的发生，这些介质驱动炎症细胞在关节内的募集和滞留。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，从而确定了特定的成纤维细胞亚群，定义了以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的观点，并为其在炎症性关节病理学中的作用提供了独特的见解。在这篇综述中，我们讨论了最近在理解成纤维细胞异质性如何导致类风湿关节炎关节病理学方面的进展。最后，我们探讨了这些见解如何为未来开发直接靶向成纤维细胞选择性群体的新型疗法提供可能性。
