University of Groningen, University Medical Centre Groningen, Department of Internal Medicine, Division of Vascular Medicine.
University of Groningen, University Medical Centre Groningen, Department of Rheumatology and Clinical Immunology.
Rheumatology (Oxford). 2023 Feb 1;62(2):535-545. doi: 10.1093/rheumatology/keac410.
SSc is a multiphase autoimmune disease with a well-known triad of clinical manifestations including vasculopathy, inflammation and fibrosis. Although a plethora of drugs has been suggested as potential candidates to halt SSc progression, nothing has proven clinically efficient. In SSc, both innate and adaptive immune systems are abnormally activated fuelling fibrosis of the skin and other vital organs. Macrophages have been implicated in the pathogenesis of SSc and are thought to be a major source of immune dysregulation. Due to their plasticity, macrophages can initiate and sustain chronic inflammation when classically activated while, simultaneously or parallelly, when alternatively activated they are also capable of secreting fibrotic factors. Here, we briefly explain the polarization process of macrophages. Subsequently, we link the activation of macrophages and monocytes to the molecular pathology of SSc, and illustrate the interplay between macrophages and fibroblasts. Finally, we present recent/near-future clinical trials and discuss novel targets related to macrophages/monocytes activation in SSc.
系统性硬化症（SSc）是一种多相自身免疫性疾病，具有众所周知的三联征临床特征，包括血管病变、炎症和纤维化。尽管已经提出了大量药物作为潜在的候选药物来阻止 SSc 的进展，但没有一种药物在临床上被证明是有效的。在 SSc 中，先天和适应性免疫系统都异常激活，导致皮肤和其他重要器官的纤维化。巨噬细胞被认为与 SSc 的发病机制有关，并且被认为是免疫失调的主要来源。由于其可塑性，巨噬细胞在经典激活时可以引发和维持慢性炎症，而在同时或平行时，当它们被替代激活时，也能够分泌纤维化因子。在这里，我们简要解释巨噬细胞的极化过程。随后，我们将巨噬细胞和单核细胞的激活与 SSc 的分子病理学联系起来，并说明巨噬细胞和成纤维细胞之间的相互作用。最后，我们介绍了最近/即将进行的临床试验，并讨论了与 SSc 中巨噬细胞/单核细胞激活相关的新靶点。
