Cutolo Maurizio, Soldano Stefano, Smith Vanessa, Gotelli Emanuele, Hysa Elvis
Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genova, Italy.
IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Nat Rev Rheumatol. 2025 Jul 28. doi: 10.1038/s41584-025-01279-w.
Macrophages regulate inflammatory and fibrotic processes in several autoimmune and inflammatory rheumatic diseases. They are highly plastic cells, shifting within a range of pro-inflammatory and anti-inflammatory or pro-fibrotic phenotypes in response to dynamic interactions with other cells, environmental factors and cytokine signatures. The terms 'M1 macrophages', or classically activated, and 'M2 macrophages', or alternatively activated, were previously used to denote pro- and anti-inflammatory macrophage subsets, respectively, but this classification system has been outdated by in vivo evidence of a continuum of macrophage phenotypes that includes M1-like, M2-like and hybrid phenotypes. Deciphering the specific mechanisms that drive macrophage plasticity and function during the progression of rheumatoid arthritis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematosus, and in synovitis and large vessel vasculitis in polymyalgia rheumatica and giant-cell arteritis, can improve our understanding of disease pathophysiology. Macrophage plasticity is enhanced in synovial tissue in rheumatoid arthritis, fibrotic skin and lung in systemic sclerosis, damaged kidney in systemic lupus erythematosus, and the bursal tissues or large vessels in polymyalgia rheumatica and giant-cell arteritis. Sophisticated transcriptomic analyses have revealed various phenotypic clusters of macrophages in biopsies of affected organs. Moreover, macrophage plasticity seems to be targeted by some standardized drugs used to treat the aforementioned conditions.
巨噬细胞在多种自身免疫性和炎性风湿性疾病中调节炎症和纤维化过程。它们是高度可塑性的细胞，会根据与其他细胞、环境因素和细胞因子特征的动态相互作用，在一系列促炎、抗炎或促纤维化表型之间转变。术语“M1巨噬细胞”（即经典激活的巨噬细胞）和“M2巨噬细胞”（即替代激活的巨噬细胞）以前分别用于表示促炎和抗炎巨噬细胞亚群，但这一分类系统已因体内证据表明巨噬细胞表型是连续的，包括M1样、M2样和混合表型而过时。在类风湿关节炎、银屑病关节炎、系统性硬化症、系统性红斑狼疮以及风湿性多肌痛和巨细胞动脉炎的滑膜炎和大血管血管炎进展过程中，解读驱动巨噬细胞可塑性和功能的具体机制，有助于我们更好地理解疾病的病理生理学。在类风湿关节炎的滑膜组织、系统性硬化症的纤维化皮肤和肺部、系统性红斑狼疮受损的肾脏以及风湿性多肌痛和巨细胞动脉炎的滑囊组织或大血管中巨噬细胞可塑性增强。精密的转录组分析揭示了受影响器官活检中巨噬细胞的各种表型簇。此外，巨噬细胞可塑性似乎是用于治疗上述病症的一些标准化药物的作用靶点。
