内质网应激相关调控机制在免疫反应与疾病中的作用

The role of endoplasmic reticulum stress-related regulatory mechanisms in immune response and diseases

内质网是负责细胞蛋白质翻译后修饰和折叠的细胞工厂,然而由于受到一些内、外源性因素的刺激,内质网功能会受到干扰,蛋白质加工运输受到阻碍,未折叠或错误折叠的蛋白质在内质网中不断累积,引起内质网应激。而这种情况出现后,会激活未折叠蛋白反应来降低内质网应激的程度,使内质网生理活动恢复到稳态。当刺激持续存在或过于强烈,就会引发自噬途径来降解蛋白,进而起到维持稳态的作用。近年来的研究发现,未折叠蛋白反应三个相关途径不仅与固有免疫反应的信号转导途径有很大关联,而且还会通过调控免疫细胞来参与免疫反应。除此以外,这三个通路及其相关因子的调控与神经退行性疾病、代谢相关疾病、肝脏疾病等联系紧密。本文将近年来内质网应激相关机制在免疫以及相关疾病中的重要作用进行综述,为今后研究人员在开展相关研究时提供一些思路和参考。

The endoplasmic reticulum(ER)takes part in the post-translational modification and folding of native protein.Due to the internal or external stimulations,the function of the endoplasmic reticulum can be interrupted to some degree,leading to serious impairment of protein processing and transportation.With the accumulation of the unfolded or misfolded proteins,ER can display some biological responses,termed as ER stress.If ER stress occurs,the unfolded protein response could be stimulated to recover the normal homeostasis of ER.When the stimulus persists or is too strong,it will trigger the autophagy pathway to degrade the protein,which in turn plays a role in maintaining homeostasis.In recent years,it has been found that the three related pathways of the unfolded protein response are not only closely related to the signaling pathways of the innate immune response,but also participate in the immune response by regulating immune cells.In addition,the regulation of these three pathways and their related factors is closely related to neurodegenerative diseases,metabolism-related diseases,liver diseases and so on.In this review,molecular mechanisms for ER stress will be summarized systematically to give new insights into therapy for diseases in future.