[Regulation of immune cell function by the unfolded protein response and its underlying mechanisms]

The unfolded protein response (UPR) serves as a pivotal regulatory mechanism that enables cells to mitigate endoplasmic reticulum proteostasis disturbance. The evolutionarily conserved pathway encompasses three core signalings, namely the inositol-requiring enzyme 1α-X-Box-protein-1s (IRE1α-XBP1s), protein kinase RNA-like endoplasmic reticulum kinase-eukaryotic initiation factor-2α-activating transcription factor 4 (PERK-eIF2α-ATF4), and activating transcription factor 6 (ATF6) pathways. Notably, the activation of UPR pathway modulates the phenotype and functional properties of immune cells, and is intricately involved in the pathogenesis and progression of diverse immune-related disorders. In this review, we provide a systematic overview of the molecular mechanisms underlying UPR activation in different immune cell subsets, and further delve into the regulatory roles of UPR signaling in the survival, development, differentiation, and effector functions of immune cells. Collectively, this review aims to provide a theoretical framework for comprehensively elucidating the pivotal roles of UPR in immune responses and the pathogenesis of immune-related diseases.