Control of immune cell function by the unfolded protein response

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.

Automated summary

Initiating and maintaining optimal immune responses requires the endoplasmic reticulum's orchestration of protein synthesis and processing in leukocytes. Dysregulation of the unfolded protein response (UPR) in immune cells can lead to various pathologies. This review explores the role of UPR in immune cells and discusses how modulating this pathway could be used therapeutically.