The endoplasmic reticulum ER plays crucial roles in cellular processes such as lipid biosynthesis, intracellular calcium homeostasis and protein folding. Several sources of stress can perturb ER homeostasis, leading to the accumulation of unfolded proteins in its lumen. This subsequently triggers a signal transduction cascade known as the unfolded protein response (UPR). The UPR is primarily an adaptive mechanism aiming to protect cells from protein aggregates and to restore ER functions. However, if sustained, the UPR can exacerbate inflammation and it has been implicated in the genesis and progression of pathologies such as obesity, type 1 and type 2 diabetes, cancer, neurodegenerative and autoimmune diseases.

In immune cells, UPR molecular effectors are also involved in regulating physiological functions such as cell differentiation, survival, and immunoglobulin and cytokine production. Recently, the UPR machinery has been shown to modulate the maturational program and the antigen presentation capacities of dendritic cells. Taken together, it is now evident that the UPR plays an important role in orchestrating a variety functions of the immune system, both as part of normal immune cell physiology as well as in the modulation of established immune responses.

In this Research Topic we aim to look at the recent advances in our understanding of the mechanisms and significance of ER stress and the UPR in immunity. We welcome the submission of high-quality Original Research, Brief Research Reports, Reviews and Mini-Reviews covering, but not limited to, the following topics:

1. The role of UPR effectors in immune cell homeostasis.
2. ER stress and UPR effectors in immune cell dysfunction.
3. ER stress in infection and chronic inflammatory diseases.
4. ER stress in the breaking of immune tolerance: involvement in the pathogenesis of autoimmune diseases.
5. ER stress as a trigger/enhancer of inflammation in neuropathologies, neurodegenerative and psychiatric diseases.
6. UPR effectors as new pharmacological targets for the modulation of inflammatory/immune responses.

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Frontiers in Immunology

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