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Inflammatory signals emerging from the endoplasmic reticulum

Final Report Summary - ERINFLAMMATION (Inflammatory signals emerging from the endoplasmic reticulum)

Loss of cellular integrity is a hallmark of severe pathogenic insults and leads to the activation of immune programs aimed at restoring tissue homeostasis and fighting infections. With this ERC grant we investigated stress pathways that regulated immune responses. We characterized pathways such as those stemming from the endoplasmic reticulum stress, eEF2k and the integrated stress response, and studied their contribution to physiological processes including inflammation. In particular, we identified a new stress pathway that was engaged upon alterations of the Nuclear Envelope (NE). We found that this immune response was characterized by the secretion of inflammatory mediators such as IL-1. We identified the AIM2 inflammasome as the main sensor involved in the production of IL-1 upon NE-stress. Overall these findings opened new avenues of research directed at understanding the role of stress pathways including NE stress in autoinflammatory diseases, aging and cancer.