Intestinal homeostasis is achieved by the balance among intestinal epithelium, immune cells, and gut microbiota. Gasdermins (GSDMs), a family of membrane pore forming proteins, can trigger rapid inflammatory cell death in the gut, mainly pyroptosis and NETosis. Importantly, there is increasing literature on the non-cell lytic roles of GSDMs in intestinal homeostasis and disease. While GSDMA is low and PJVK is not expressed in the gut, high GSDMB and GSDMC expression is found almost restrictively in intestinal epithelial cells. Conversely, GSDMD and GSDME show more ubiquitous expression among various cell types in the gut. The N-terminal region of GSDMs can be liberated for pore formation by an array of proteases in response to pathogen- and danger-associated signals, but it is not fully understood what cell type-specific mechanisms activate intestinal GSDMs. The host relies on GSDMs for pathogen defense, tissue tolerance, and cancerous cell death; however, pro-inflammatory milieu caused by pyroptosis and excessive cytokine release may favor the development and progression of inflammatory bowel disease and cancer. Therefore, a thorough understanding of spatiotemporal mechanisms that control gasdermin expression, activation, and function is essential for the development of future therapeutics for intestinal disorders.

肠道稳态是通过肠上皮、免疫细胞和肠道微生物群之间的平衡来实现的。Gasdermins (GSDMs) 是一类膜孔形成蛋白，可引发肠道内炎症细胞快速死亡，主要是焦亡和NETosis 。重要的是，关于 GSDM 在肠道稳态和疾病中的非细胞溶解作用的文献越来越多。虽然 GSDMA 较低且 PJVK 在肠道中不表达，但 GSDMB 和 GSDMC 的高表达几乎仅限于肠上皮细胞。相反，GSDMD 和 GSDME 在肠道各种细胞类型中表现出更普遍的表达。响应病原体和危险相关信号，一系列蛋白酶可以释放 GSDM 的 N 末端区域以形成孔，但尚不完全了解什么细胞类型特异性机制激活肠道 GSDM。宿主依靠 GSDM 来防御病原体、组织耐受和癌细胞死亡；然而，焦亡和过度细胞因子释放引起的促炎环境可能有利于炎症性肠病和癌症的发生和进展。因此，彻底了解控制gasdermin表达、激活和功能的时空机制对于开发未来肠道疾病疗法至关重要。