中国科学院分子细胞科学卓越创新中心孙兵等研究人员合作发现，过敏原蛋白酶激活的应激颗粒组装和gasdermin D的片段化控制白细胞介素-33的分泌。2022年7月6日，《自然—免疫学》杂志在线发表了这项成果。

研究人员发现两个细胞事件是接触过敏原后分泌白细胞介素-33（IL-33）的基础。首先，由过敏原激活的应激颗粒组装许可了IL-33的核-细胞质运输，但没有许可IL-33的分泌。其次，一种新形式的小鼠氨基端p40片段gasdermin D（Gsdmd），其生成与炎症性caspase-1和caspase-11无关，通过在细胞膜上形成孔来主导IL-33的细胞质分泌。阻断应激颗粒的组装或通过残基309-313的氨基酸突变（ELRQQ）废除p40的产生，都能有效地防止小鼠上皮细胞中IL-33的释放。这些研究结果表明，针对应激颗粒的分解和Gsdmd的片段化可以减少IL-33依赖的过敏性气道炎症。

据悉，IL-33是一种上皮细胞来源的细胞因子，对环境损伤反应迅速，在启动气道炎症性疾病方面有关键作用。然而，过敏原暴露后IL-33分泌的分子机制还不清楚。

附：英文原文

Title: Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion

Author: Chen, Wen, Chen, Shuangfeng, Yan, Chenghua, Zhang, Yaguang, Zhang, Ronghua, Chen, Min, Zhong, Shufen, Fan, Weiguo, Zhu, Songling, Zhang, Danyan, Lu, Xiao, Zhang, Jia, Huang, Yuying, Zhu, Lin, Li, Xuezhen, Lv, Dawei, Fu, Yadong, Iv, Houkun, Ling, Zhiyang, Ma, Liyan, Jiang, Hai, Long, Gang, Zhu, Jinfang, Wu, Dong, Wu, Bin, Sun, Bing

Issue&Volume: 2022-07-06

Abstract: Interleukin-33 (IL-33), an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammatory diseases. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we found that two cell events were fundamental for IL-33 secretion after exposure to allergens. First, stress granule assembly activated by allergens licensed the nuclear-cytoplasmic transport of IL-33, but not the secretion of IL-33. Second, a neo-form murine amino-terminal p40 fragment gasderminD (Gsdmd), whose generation was independent of inflammatory caspase-1 and caspase-11, dominated cytosolic secretion of IL-33 by forming pores in the cell membrane. Either the blockade of stress granule assembly or the abolishment of p40 production through amino acid mutation of residues 309–313 (ELRQQ) could efficiently prevent the release of IL-33 in murine epithelial cells. Our findings indicated that targeting stress granule disassembly and Gsdmd fragmentation could reduce IL-33-dependent allergic airway inflammation.

DOI: 10.1038/s41590-022-01255-6

Source: https://www.nature.com/articles/s41590-022-01255-6