启动和维持最佳免疫反应需要白细胞高水平的蛋白质合成、折叠、修饰和转运，这些过程被内质网协同调控。重要的是，多种细胞外和细胞内条件都可能削弱内质网的蛋白质处理能力，导致“内质网应激”状态并激活展开蛋白质反应(UPR)。新近证据表明，生理或病理激活UPR可以对免疫细胞的存活、代谢、功能和命运产生效应。在本综述中，我们讨论适应性UPR在免疫细胞中的经典作用以及该通路在白细胞中的失调如何导致癌症、自身免疫和代谢紊乱等多种病理。此外，我们概述药理调节UPR可如何被利用来控制或激活疾病中的免疫细胞功能。 © 2023年，Springer Nature有限公司。

Initiating and maintaining optimal immune responses requires high levels of protein synthesis, folding, modification and trafficking in leukocytes, which are processes orchestrated by the endoplasmic reticulum. Importantly, diverse extracellular and intracellular conditions can compromise the protein-handling capacity of this organelle, inducing a state of 'endoplasmic reticulum stress' that activates the unfolded protein response (UPR). Emerging evidence shows that physiological or pathological activation of the UPR can have effects on immune cell survival, metabolism, function and fate. In this Review, we discuss the canonical role of the adaptive UPR in immune cells and how dysregulation of this pathway in leukocytes contributes to diverse pathologies such as cancer, autoimmunity and metabolic disorders. Furthermore, we provide an overview as to how pharmacological approaches that modulate the UPR could be harnessed to control or activate immune cell function in disease.© 2023. Springer Nature Limited.