Gasdermins (GSDM) are a family of six homologous proteins (GSDMA to E and Pejvakin) in humans. GSDMA-E are pore-forming proteins targeting the plasma membrane to trigger a rapid cell death termed pyroptosis or bacterial membranes to promote antibacterial immune defenses. Activation of GSDM relies on a proteolytic cleavage but is highly dependent on GSDM expression levels. The different GSDM genes have tissue-specific expression pattern although metabolic, environmental signals, cell stress and numerous cytokines modulate their expression levels in tissues. Furthermore, expression of GSDM genes can be modulated by polymorphisms and have been associated with susceptibility to asthma, inflammatory bowel diseases and rhinovirus wheezing illness. Finally, the expression level of GSDMs controls the balance between apoptosis and pyroptosis affecting both the response and the toxicity to chemotactic drugs and antitumoral treatments. Numerous cancer demonstrate positive or negative modulation of GSDM expression levels correlating with distinct tumor-specific prognosis. In this review, we present the transcriptional and epigenetic mechanisms controlling GSDM levels and their functional consequences in asthma, infection, cancers and inflammatory bowel disease to highlight how this first layer of regulations has key consequences on disease susceptibility and response to treatment.

Gasdermins (GSDM) 是人类中六种同源蛋白（GSDMA 到 E 和 Pejvakin）的家族。GSDMA-E 是靶向质膜的成孔蛋白，可触发细胞快速死亡，称为细胞焦亡或细菌膜，以促进抗菌免疫防御。GSDM 的激活依赖于蛋白水解切割，但高度依赖于 GSDM 表达水平。不同的 GSDM 基因具有组织特异性表达模式，尽管代谢、环境信号、细胞应激和众多细胞因子调节它们在组织中的表达水平。此外，GSDM的表达基因可以通过多态性进行调节，并且与哮喘、炎症性肠病和鼻病毒喘息病的易感性有关。最后，GSDMs 的表达水平控制细胞凋亡和细胞焦亡之间的平衡，影响对趋化药物和抗肿瘤治疗的反应和毒性。许多癌症表现出与不同肿瘤特异性预后相关的GSDM表达水平的正向或负向调节。在这篇综述中，我们介绍了控制GSDM的转录和表观遗传机制水平及其在哮喘、感染、癌症和炎症性肠病中的功能后果，以突出第一层法规如何对疾病易感性和对治疗的反应产生关键影响。