IL-1β secretion depended on RIPK3 and partly on caspase-1/-11, and based on the proteolytic activation of caspase-8 may additionally involve caspase-8-mediated processing of pro-IL-1β, as reported previously.35 In contrast to macrophages and DCs, however, neutrophils were shown to secrete IL-1β without undergoing pyroptosis.49 These data suggest that Xiap−/− neutrophils may contribute to hyperinflammation and progression in certain pathologies seen in X-linked lymphoproliferative syndrome 2 patients. This evidence concerns the gene RIPK3 and X-linked lymphoproliferative disease.