Integrated stress response-altered pro-inflammatory signals in mucosal immune-related cells

Various cells are associated with the integrated stress response (ISR) that leads to translation arrest via phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Pathogenic insults or nutritional imbalance in the mucosal tissues including the intestinal, airway, and genitourinary epithelia can cause ISRs, which have been linked to different mucosal inflammatory responses and subsequent systemic diseases. In particular, translational arrest caused by the early recognition of luminal microbes as well as nutritional status allows the human body to mount appropriate responses and maintain homeostasis both at the cellular and systemic levels. However, an over- or reduced ISR can create pathogenic conditions such as inflammation and carcinogenesis. This present review explores the association between eIF2α kinase-linked pathways and mucosal or systemic pro-inflammatory signals activated by xenobiotic insults (such as ones caused by microbes or nutritional abnormalities). Understanding ISR-modulated cellular alterations will provide progressive insights into approaches for treating human mucosal inflammatory and metabolic disorders.