新型翻译后修饰调控固有免疫应答及其在炎症性疾病中的研究进展

The Role of New Post-Translational Modifications in Regulation of Innate Immune Response and Inflammatory Diseases:a Comprehensive Review

翻译后修饰(post-translational modifications,PTMs)是指特定的化学基团或蛋白质共价偶联到一个或多个氨基酸残基上的一种化学修饰,具有调节蛋白构象、活性、亚细胞定位及蛋白相互作用等功能。固有免疫是抵御病原体感染的第一道防线,但其异常活化与慢性炎症性疾病的发生发展密切相关。在此过程中,PTM通过调控关键信号蛋白的募集、稳定、基因转录等多个方面对固有免疫信号进行精确调控。近年来,除了磷酸化、泛素化等经典的PTM外,新型PTM如类泛素化修饰、ADP-核糖基化修饰、由细胞内小分子代谢物(例如:乳酸、琥珀酸、棕榈酸等)介导的修饰以及糖基化修饰同样参与调控固有免疫应答,其在炎症性疾病中的作用越来越受到关注。该文重点阐述了新型PTM调控固有免疫信号的重要作用及其在固有免疫异常活化所致的炎症性疾病中的功能。靶向异常的PTM将为自身免疫性疾病、慢性炎症疾病或感染性疾病的防治提供新的视角和思路。

PTMs(post-translational modifications)refer to the chemical modification alterations of proteins which are covalently conjugated with centain chemical groups or proteins.PTMs play essential roles in modulating the conformation,activity,subcellular localization and protein-protein interactions of target proteins.Innate immunity is the first line of defense against infection,and its abnormal activation is closely related to the pathogenesis of chronic inflammatory diseases.In this process,PTMs precisely regulate innate immune response by modulating the recruitment,stabilization,and transcription of key signaling proteins.In addition to classic PTMs(including phosphorylation,ubiquitination,etc.),some new PTMs,such as ubiquitin-like modification,ADP-ribosylation and metabolites(lactate,succinate,palmitate,etc.)-mediated modifications,glycosylation,have been recently revealed to regulate innate immune response and be involved in the development of inflammatory diseases.This review mainly focuses on discussing the regulatory mechanism of new PTMs in innate immune signaling and their functions in inflammatory diseases caused by abnormal activation of innate immunity.