STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD

SAVI preclinical mouse model in which immune-cell-driven pathology and lethality are rescued by receptor-interacting serine/threonine-protein kinase 3 (Ripk3) co-deletion. These findings establish STING-driven ZBP1-mediated necroptosis as a central pathogenic mechanism in both caspase-8-deficient inflammation and SAVI and suggest that targeting the ZBP1-RIPK3-MLKL axis holds therapeutic potential for interferonopathies characterized by excessive necroptosis.