Systemic sclerosis (SSc) is a prototypical inflammatory fibrotic disease involving inflammation, vascular abnormalities and fibrosis that primarily affect the skin and lungs. The aetiology of SSc is unknown and its pathogenesis is only partially understood. Of all the rheumatic diseases, SSc carries the highest all-cause mortality rate and represents an unmet medical need. A growing body of evidence implicates epigenetic aberrations in this intractable disease, including specific modifications affecting the three main cell types involved in SSc pathogenesis: immune cells, endothelial cells and fibroblasts. In this Review, we discuss the latest insights into the role of DNA methylation, histone modifications and non-coding RNAs in SSc and how these epigenetic alterations affect disease features. In particular, histone modifications have a role in the regulation of gene expression pertinent to activation of fibroblasts to myofibroblasts, governing their fate. DNA methyltransferases are crucial in disease pathogenesis by mediating methylation of DNA in specific promoters, regulating expression of specific pathways. We discuss targeting of these enzymes for therapeutic gain. Innovative epigenetic therapy could be targeted to treat the disease in a precision epigenetics approach.

系统性硬化症 (SSc) 是一种典型的炎症性纤维化疾病，涉及主要影响皮肤和肺部的炎症、血管异常和纤维化。SSc 的病因尚不清楚，其发病机制仅部分了解。在所有风湿性疾病中，SSc 的全因死亡率最高，代表了未满足的医疗需求。越来越多的证据表明这种顽固性疾病存在表观遗传异常，包括影响 SSc 发病机制中涉及的三种主要细胞类型的特定修饰：免疫细胞、内皮细胞和成纤维细胞。在这篇综述中，我们讨论了关于 DNA 甲基化、组蛋白修饰和非编码 RNA 在 SSc 中的作用以及这些表观遗传改变如何影响疾病特征的最新见解。特别是，组蛋白修饰在调节与成纤维细胞激活成肌成纤维细胞相关的基因表达中发挥作用，控制它们的命运。DNA甲基转移酶通过介导特定启动子中DNA的甲基化，调节特定途径的表达，在疾病发病机制中至关重要。我们讨论了靶向这些酶以获得治疗效果。创新的表观遗传学疗法可以通过精确的表观遗传学方法靶向治疗该疾病。