Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Allergy. 2024 Sep;79(9):2380-2395. doi: 10.1111/all.16236. Epub 2024 Jul 14.
Pyroptosis is an inflammatory form of programmed cell death that is distinct from necrosis and apoptosis. Pyroptosis is primarily mediated by the gasdermin family of proteins (GSDMA-E and PVJK), which, when activated by proteolytic cleavage, form pores in the plasma membrane, leading to cell death. While much of the past research on pyroptosis has focused on its role in cancer, metabolic disorders, and infectious diseases, recent experimental and observational studies have begun to implicate pyroptosis in allergic diseases. These studies suggest that gasdermin-mediated pyroptosis contributes to the development of allergic conditions and could offer novel targets for therapy. Here, we review our current understanding of pyroptosis with an emphasis on the role of gasdermins as executioners of pyroptosis and potential mediators to allergic disease. We highlight new discoveries that establish a mechanistic link between the biochemical actions of gasdermins and the onset of allergic diseases. Additionally, we discuss how pyroptosis and gasdermins might contribute to the dysfunction of epithelial barrier, a key factor believed to initiate the progression of various allergic diseases.
细胞焦亡是一种区别于细胞坏死和细胞凋亡的炎症性程序性细胞死亡形式。细胞焦亡主要由gasdermin 家族蛋白(GSDMA-E 和 PVJK)介导,这些蛋白在被蛋白水解切割激活后,在质膜上形成孔,导致细胞死亡。虽然过去对细胞焦亡的研究主要集中在其在癌症、代谢紊乱和传染病中的作用,但最近的实验和观察性研究开始将细胞焦亡与过敏疾病联系起来。这些研究表明,gasdermin 介导的细胞焦亡有助于过敏状态的发展,并可能为治疗提供新的靶点。在这里,我们回顾了我们目前对细胞焦亡的理解,重点介绍了 gasdermins 作为细胞焦亡执行者的作用以及其作为潜在的过敏疾病介质的作用。我们强调了新的发现,这些发现确立了 gasdermins 的生化作用与过敏疾病发生之间的机制联系。此外,我们还讨论了细胞焦亡和 gasdermins 如何导致上皮屏障功能障碍,上皮屏障功能障碍被认为是各种过敏疾病进展的关键因素。