Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.
Autoimmun Rev. 2021 Mar;20(3):102758. doi: 10.1016/j.autrev.2021.102758. Epub 2021 Jan 18.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting joints and causing progressive damage and disability. Macrophages are of critical importance in the initiation and perpetuation of synovitis in RA, they can function as antigen presenting cells leading to T-cell dependent B-cell activation, assume a variety of inflammatory cell states with the production of destructive cytokines, but also contribute to tissue homeostasis/repair. The recent development of high-throughput technologies, including bulk and single cells RNA-sequencing, has broadened our understanding of synovial cell diversity, and opened novel perspectives to the discovery of new potential therapeutic targets in RA. In this review, we will focus on the relationship between the synovial macrophage infiltration and clinical disease severity and response to treatment. We will then provide a state-of-the-art picture of the biological roles of synovial macrophages and distinct macrophage subsets described in RA. Finally, we will review the effects of approved conventional and biologic drugs on the synovial macrophage component and highlight the therapeutic potential of future strategies to re-program macrophage phenotypes in RA.
类风湿关节炎（RA）是一种慢性炎症性自身免疫性疾病，影响关节并导致进行性损伤和残疾。巨噬细胞在 RA 滑膜炎症的启动和持续中至关重要，它们可以作为抗原提呈细胞，导致 T 细胞依赖性 B 细胞激活，产生具有破坏性细胞因子的各种炎症细胞状态，但也有助于组织稳态/修复。高通量技术（包括批量和单细胞 RNA 测序）的最新发展拓宽了我们对滑膜细胞多样性的理解，并为 RA 中发现新的潜在治疗靶点开辟了新的视角。在这篇综述中，我们将重点关注滑膜巨噬细胞浸润与临床疾病严重程度和治疗反应之间的关系。然后，我们将提供 RA 中描述的滑膜巨噬细胞和不同巨噬细胞亚群的生物学作用的最新概述。最后，我们将回顾已批准的常规和生物药物对滑膜巨噬细胞成分的影响，并强调未来在 RA 中重新编程巨噬细胞表型的治疗策略的治疗潜力。
