美国康涅狄格大学Vijay A. Rathinam小组发现，gasdermin孔通过细胞外囊泡转移将焦亡传播到旁观细胞。相关论文于2024年12月31日在线发表在《细胞》杂志上。

研究人员表示，由gasdermin（GSDM）介导的焦亡在感染和炎症中发挥着重要作用。焦亡会触发包括损伤相关分子模式（DAMP）在内的炎症分子的释放。然而，焦亡的后果，特别是除白介素（IL）-1细胞因子和DAMP外，如何调控炎症仍不明确。

研究人员展示了焦亡的细胞间传播，从死亡细胞到旁观细胞，以及在体外和体内的传播。研究人员发现由焦亡细胞释放的细胞外囊泡（EV），是将切割性死亡传播给其他细胞的载体，从而促进炎症。DNA-PAINT超分辨率和免疫电子显微镜揭示了焦亡细胞释放的EV上的GSDMD孔结构。重要的是，焦亡的EV将GSDMD孔转移到旁观细胞的质膜上并使其死亡。

总体而言，研究人员证明了细胞间囊泡转移GSDMD孔来传播焦亡，并揭示了类似多米诺效应的机制以调控与疾病相关的旁观细胞死亡。

附：英文原文

Title: Transplantation of gasdermin pores by extracellular vesicles propagates pyroptosis to bystander cells

Author: Skylar S. Wright, Puja Kumari, Víctor Fraile-ágreda, Chengliang Wang, Sonia Shivcharan, Shirin Kappelhoff, Eleonora G. Margheritis, Alyssa Matz, Swathy O. Vasudevan, Ignacio Rubio, Michael Bauer, Beiyan Zhou, Sivapriya Kailasan Vanaja, Katia Cosentino, Jianbin Ruan, Vijay A. Rathinam

Issue&Volume: 2024-12-31

Abstract: Pyroptosis mediated by gasdermins (GSDMs) plays crucial roles in infection and inflammation. Pyroptosis triggers the release of inflammatory molecules, including damage-associated molecular patterns (DAMPs). However, the consequences of pyroptosis—especially beyond interleukin (IL)-1 cytokines and DAMPs—that govern inflammation are poorly defined. Here, we show intercellular propagation of pyroptosis from dying cells to bystander cells in vitro and in vivo. We identified extracellular vesicles (EVs) released by pyroptotic cells as the propagator of lytic death to naive cells, promoting inflammation. DNA-PAINT super-resolution and immunoelectron microscopy revealed GSDMD pore structures on EVs released by pyroptotic cells. Importantly, pyroptotic EVs transplant GSDMD pores on the plasma membrane of bystander cells and kill them. Overall, we demonstrate that cell-to-cell vesicular transplantation of GSDMD pores disseminates pyroptosis, revealing a domino-like effect governing disease-associated bystander cell death.

DOI: 10.1016/j.cell.2024.11.018

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01334-5