Bai Yang, Pan Youdong, Liu Xing
Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Rev Mol Cell Biol. 2025 Mar 24. doi: 10.1038/s41580-025-00837-0.
Pyroptosis, a novel mode of inflammatory cell death, is executed by membrane pore-forming gasdermin (GSDM) family members in response to extracellular or intracellular injury cues and is characterized by a ballooning cell morphology, plasma membrane rupture and the release of inflammatory mediators such as interleukin-1β (IL-1β), IL-18 and high mobility group protein B1 (HMGB1). It is a key effector mechanism for host immune defence and surveillance against invading pathogens and aberrant cancerous cells, and contributes to the onset and pathogenesis of inflammatory and autoimmune diseases. Manipulating the pore-forming activity of GSDMs and pyroptosis could lead to novel therapeutic strategies. In this Review, we discuss the current knowledge regarding how GSDM-mediated pyroptosis is initiated, executed and regulated, its roles in physiological and pathological processes, and the crosstalk between different modes of programmed cell death. We also highlight the development of drugs that target pyroptotic pathways for disease treatment.
细胞焦亡是一种新型的炎症性细胞死亡方式，由膜打孔形成的gasdermin（GSDM）家族成员响应细胞外或细胞内损伤信号而执行，其特征为细胞呈气球样形态、质膜破裂以及炎性介质如白细胞介素-1β（IL-1β）、IL-18和高迁移率族蛋白B1（HMGB1）的释放。它是宿主免疫防御以及监测入侵病原体和异常癌细胞的关键效应机制，并参与炎症和自身免疫性疾病的发生及发病过程。操控GSDM的打孔活性和细胞焦亡可能会带来新的治疗策略。在本综述中，我们讨论了关于GSDM介导的细胞焦亡如何启动、执行和调节的现有知识，其在生理和病理过程中的作用，以及不同程序性细胞死亡模式之间的相互作用。我们还重点介绍了针对细胞焦亡途径进行疾病治疗的药物开发情况。
