中国科学院分子细胞科学卓越创新中心陈玲玲研究团队发现核应激体从头组装重排并增强NFIL3以抑制急性炎症反应。这一研究成果发表在2025年5月27日出版的国际学术期刊《细胞》上。
该团队报道了SatⅢdna、SatⅢrna和30nSB蛋白在应激后不久组装成组织良好的结构。活化的SatⅢ异染色质位点迅速扩大，导致空间距离减少，邻近基因的表达增强，包括转录抑制因子NFIL3，已知其可抑制促炎细胞因子的产生。NFIL3基因座在nSB区域内的重排增强了NFIL3染色质的可及性，使NFIL3启动子更容易被转录因子热休克转录因子1 （HSF1）和含溴结构域4 （BRD4）所接近，这些转录因子在逆境下也会被nSB招募。人外周血单核细胞（PBMC）来源的巨噬细胞在热休克加病原体相关分子模式处理下表现出升高的SatⅢ和NFIL3表达，后者抑制关键的炎症细胞因子。重要的是，在脓毒症患者中，NFIL3表达与SatⅢ激活呈正相关，这一过程与患者生存呈正相关，突出了nSBs在抑制炎症反应中的作用。
据介绍，以satellite III (SatIII) RNAs为标志的无膜核应激体（nSBs）存在于灵长类动物的应激感知中。
附：英文原文
Title: De novo assembly of nuclear stress bodies rearranges and enhances NFIL3 to restrain acute inflammatory responses
Author: Xiao-Qi Liu, Pan Li, Bao-Qing Gao, Heng-Le Zhu, Liang-Zhong Yang, Yang Wang, Yu-Yao Zhang, Hao Wu, Yu-Hang Pan, Lin Shan, Hongtao Yu, Li Yang, Ling-Ling Chen
Issue&Volume: 2025-05-27
Abstract: The membrane-less nuclear stress bodies (nSBs), with satellite III (SatIII) RNAs as the hallmark, are present in primates upon sensing stresses. We report that SatⅢ DNAs, SatⅢ RNAs, and 30 nSB proteins assemble into well-organized structures shortly after stresses. The activated SatⅢ heterochromatin loci rapidly expand, resulting in reduced spatial distance and enhanced expression of adjacent genes, including the transcription suppressor NFIL3, which is known to dampen proinflammatory cytokine production. Rearranging NFIL3 loci within the nSB territory enhances NFIL3 chromatin accessibility and makes NFIL3 promoters more accessible to transcription factors heat shock transcription factor 1 (HSF1) and bromodomain containing 4 (BRD4), which are also recruited to nSBs upon stresses. Human peripheral blood mononuclear cell (PBMC)-derived macrophages under heat shock plus pathogen-associated molecular pattern treatments exhibit increased SatⅢ and NFIL3 expression, the latter of which suppresses key inflammatory cytokines. Importantly, NFIL3 expression positively correlates with SatⅢ activation in septic patients, a process positively correlated to patient survival, highlighting a role of nSBs in restraining inflammatory responses.
DOI: 10.1016/j.cell.2025.05.003
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00514-8