Endoplasmic reticulum stress: A key player in immune cell regulation and autoimmune disorders

The endoplasmic reticulum (ER) is a large organelle, found in all eukaryotes, that is essential for normal cellular function. This function encompasses protein folding and quality control, post-translational modifications, lipid regulation, and the storage of intracellular calcium, among others. These diverse processes are essential for maintaining proteome stability. Therefore, a robust surveillance system is established under stress to ensure cell homeostasis. Sources of stress can originate from the cellular environment, including nutrient deprivation, hypoxia, and low pH, as well as from endogenous signals within the cell, such as metabolic challenges and increased demands for protein production. When cellular homeostasis is altered by one of these triggers, ER primary functions are altered which leads to the accumulation of misfolded proteins. These impaired proteins trigger the activation of the Unfolded Protein Response (UPR) pathway. This response aims at reducing ER stress by implementing the induction of complex programs to restore cell homeostasis. However, extended ER stress can modify the UPR response, shifting its signals from promoting survival to triggering pathways that reprogram or eliminate affected cells.