Yao Yuanjun, Wang Zehong, Li Junqin, Peng Aihong, Cao Yue, Liang Nannan, Zhang Kaiming
Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, State Key Breeding Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Center Hospital, Taiyuan, China.
Department of Laboratory Medicine, Medical Center Hospital of Qionglai City, Chengdu, China.
Exp Dermatol. 2024 Jul;33(7):e15135. doi: 10.1111/exd.15135.
Autoimmune skin disease is a kind of heterogeneous disease with complicated pathogenesis. Many factors such as genetic, infectious, environmental and even psychological factors may interact together to trigger a synergistic effect for the development of abnormal innate and adaptive immune responses. Although the exact mechanisms remain unclear, recent evidence suggests that pyroptosis plays a pivotal role in the development of autoimmune skin disease. The feature of pyroptosis is the first formation of pores in cellular membranes, then cell rupture and the release of intracellular substances and pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and IL-18. This hyperactive inflammatory programmed cell death damages the homeostasis of the immune system and advances autoimmunity. This review briefly summarises the molecular regulatory mechanisms of pyrin domain-containing protein 3 (NLRP3) inflammasome and gasdermin family, as well as the molecular mechanisms of pyroptosis, highlights the latest progress of pyroptosis in autoimmune skin disease, including systemic lupus erythematosus, psoriasis, atopic dermatitis and systemic scleroderma and attempts to identify its potential advantages as a therapeutic target or prognostic biomarker for these diseases.
自身免疫性皮肤病是一种发病机制复杂的异质性疾病。遗传、感染、环境甚至心理因素等多种因素可能相互作用，共同引发协同效应，导致先天性和适应性免疫反应异常。尽管确切机制尚不清楚，但最近的证据表明，细胞焦亡在自身免疫性皮肤病的发展中起关键作用。细胞焦亡的特征是细胞膜首先形成孔隙，然后细胞破裂，细胞内物质和促炎细胞因子如白细胞介素-1β（IL-1β）和IL-18释放。这种过度活跃的炎症程序性细胞死亡破坏了免疫系统的稳态，促进了自身免疫。本文综述了含pyrin结构域蛋白3（NLRP3）炎性小体和gasdermin家族的分子调控机制，以及细胞焦亡的分子机制，重点介绍了细胞焦亡在自身免疫性皮肤病（包括系统性红斑狼疮、银屑病、特应性皮炎和系统性硬化症）中的最新进展，并试图确定其作为这些疾病治疗靶点或预后生物标志物的潜在优势。
