Systemic Sclerosis (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.

中文翻译：

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巨噬细胞作为系统性硬化症纤维化的决定因素和调节因子


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表现，包括血管病变、炎症和纤维化。尽管有大量药物被认为是阻止 SSc 进展的潜在候选药物，但没有任何药物被证明具有临床效果。在 SSc 中，先天性和适应性免疫系统都异常激活，加剧皮肤和其他重要器官的纤维化。巨噬细胞与 SSc 的发病机制有关，并被认为是免疫失调的主要根源。由于其可塑性，巨噬细胞在经典激活时可以引发并维持慢性炎症，同时或并行，在交替激活时它们也能够分泌纤维化因子。在这里，我们简要解释一下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，我们介绍最近/不久的将来的临床试验，并讨论与 SSc 中巨噬细胞/单核细胞激活相关的新靶点。