Despite the fact that interferons (IFNs) act at mucosal surfaces, limited knowledge is available on the molecular mechanism of their mucosal functions. Our unpublished data suggest a major contribution of IFN-induced programmed necrosis to the pathogenesis of intestinal inflammation. Accordingly, IFNs promote non-apoptotic epithelial cell death, upregulation of mixed lineage kinase domain-like protein and loss of immune homeostasis. The central question of this project is if and by which pathways epithelial IFN-regulated necrosis contributes to intestinal inflammation. We aim to discover novel functions of IFNs in immune-epithelial communication that could be targeted for future therapeutic intervention.