Systemic sclerosis (SSc) is an autoimmune rheumatic disease with high mortality, which is featured by inflammation, vascular damage, and aggressive fibrosis. To date, the pathogenesis of SSc remains unclear and effective treatments are still under research. Active NLRP3 recruits downstream proteins such as ASC and caspase-1 and assembles into inflammasome, resulting in excretion of inflammatory cytokines including IL-1β and IL-18, as well as in pyroptosis mediated by gasdermin D. Various studies demonstrated that NLRP3 inflammasome might be involved in the mechanism of tenosynovitis, arthritis, fibrosis, and vascular damage. The pathophysiological changes might be due to the activation of proinflammatory Th2 cells, profibrotic M2 macrophages, B cells, fibroblasts, and endothelial cells. Here, we review the studies focused on NLRP3 inflammasome activation, its association with innate and adaptive immune cells, endothelium injury, and differentiation of fibroblasts in SSc. Furthermore, we summarize the prospect of therapy targeting NLRP3 pathway.

中文翻译：

---

NLRP3炎症小体在系统性硬化症中的作用

系统性硬化症（SSc）是一种以炎症、血管损伤和侵袭性纤维化为特征的高死亡率的自身免疫性风湿性疾病。迄今为止，SSc的发病机制仍不清楚，有效的治疗方法仍在研究中。活跃的 NLRP3 募集下游蛋白如 ASC 和 caspase-1 并组装成炎性体，导致炎性细胞因子（包括 IL-1β 和 IL-18）的排泄，以及由 gasdermin D 介导的细胞焦亡。各种研究表明，NLRP3 炎性体可能是参与腱鞘炎、关节炎、纤维化和血管损伤的机制。病理生理变化可能是由于促炎 Th2 细胞、促纤维化 M2 巨噬细胞、B 细胞、成纤维细胞和内皮细胞的激活。这里，我们回顾了侧重于 NLRP3 炎性体激活、其与先天性和适应性免疫细胞、内皮损伤以及 SSc 中成纤维细胞分化的相关研究。此外，我们总结了靶向 NLRP3 通路的治疗前景。