IRE1α/Xbp1s靶向调控NKp46改善NK细胞杀伤功能清除HIV感染细胞的思路探析  

IRE1α/Xbp1s targets and regulates NKp46 to improve the killing function of NK cells and eliminate HIV⁃infected cells

作　　者：钱洁玉 张清燕 桑锋[1,2] 杨瑶瑶 李强 QIAN Jieyu;ZHANG Qingyan;SANG Feng;YANG Yaoyao;LI Qiang(The First Affiliated Hospital of the Henan University of Traditional Chinese Medicine AIDS Testing Labora-tory,Zhengzhou,Henan,China,450000;Henan Key Laboratory of Viral Diseases Prevention and Treat-ment of Traditional Chinese Medicine,Zhengzhou,Henan,China,450000)

机构地区：[1]河南中医药大学第一附属医院艾滋病检测实验室,河南郑州450000 [2]河南省病毒性疾病中医药防治重点实验室,河南郑州450000

出　　处：《分子诊断与治疗杂志》2024年第4期591-594,共4页Journal of Molecular Diagnostics and Therapy

基　　金：河南省中医管理局国家中医临床研究基地专项课题(2021JDZY008,2021JDZY076,2021JDZY080);河南省自然科学基金项目(202300410255);河南省高等学校重点科研项目(21A360010);河南省科技攻关项目(212102311126)。

摘　　要：自然杀伤细胞的杀伤活性无MHC限制,不依赖抗体,是抵御肿瘤和病毒感染的第一道防线。肿瘤或慢性病毒感染后,固有免疫NK细胞与适应性免疫T细胞共同发挥免疫功能对抗肿瘤及感染,但由于免疫系统无法迅速根除病灶,免疫细胞内质网稳态被打破,使其无法发挥正常的免疫杀伤及清除功能,导致病情迅速恶化甚至死亡。NKp46是仅表达在NK细胞上的特异性活化受体,它直接影响NK细胞的活化程度与杀伤作用的强弱。艾滋病是一种目前无法根治的慢性传染病之一,病毒持续感染引起NK细胞内质网应激,IRE1α/Xbp1s信号通路的启动导致NKp46蛋白翻译大部分被抑制,影响NK细胞活化发挥功能,因此基于IRE1α/Xbp1s靶向调控NKp46寻求改善NK细胞杀伤功能的新靶点成为研究的新思路。Natural killer cells(NK)play an important role in maintaining the stability of the innate immune system,and serve as the first line of defense against tumors and viral infections.Following tumor devel⁃opment or chronic viral infections,both innate immune NK cells and adaptive immune T cells work together to combat their threats.However,the immune system may struggle to quickly eliminate the lesion,disrupting the endoplasmic reticulum homeostasis of immune cells and hindering their ability to function properly.NKp46 is a specific activation receptor found exclusively in NK cells,which directly influences the activation level and cy⁃totoxic strength of NK cells.AIDS is a chronic infectious disease that causes significant harm.Viral infections trigger the activation of the NK endoplasmic reticulum stress IRE1α/Xbp1s signaling pathway,leading to the suppression of NKp46 protein translation and impacting the activation and function of NK cells.Therefore,iden⁃tifying new targets to enhance NK cell function has become a current research priority and area of interest.

关 键 词：艾滋病 NK细胞 内质网稳态 NKp46 IRE1α/Xbp1s信号通路 

分 类 号：R392[医药卫生—免疫学]