Nlrp3 inflammasome activation in macrophages suffices for inducing autoinflammation in mice.

ABSTRACT: Cryopyrin-associated periodic syndromes (CAPS) are a spectrum of autoinflammatory disorders caused by gain-of-function NLRP3 mutant proteins that form hyperactive inflammasomes leading to overproduction of the pro-inflammatory cytokines IL-1β and IL-18. Expressing the murine gain-of-function Nlrp3^A350V mutant selectively in neutrophils recapitulates several autoinflammatory features of human CAPS, but the potential contribution of macrophage inflammasome hyperactivation to CAPS development is poorly defined. Here, we show that expressing Nlrp3^A350V in macrophages is sufficient for driving severe multi-organ autoinflammation leading to perinatal lethality in mice. In addition, we show that macrophages contribute to autoinflammation also in adult mice, as depleting macr

SUBMITTER: Frising UC 

PROVIDER: S-EPMC9253760 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature