Cryo-sensitive aggregation triggers NLRP3 inflammasome assembly in cryopyrin-associated periodic syndrome.

ABSTRACT: Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome caused by mutations of NLRP3 gene encoding cryopyrin. Familial cold autoinflammatory syndrome, the mildest form of CAPS, is characterized by cold-induced inflammation induced by the overproduction of IL-1β. However, the molecular mechanism of how mutated NLRP3 causes inflammasome activation in CAPS remains unclear. Here, we found that CAPS-associated NLRP3 mutants form cryo-sensitive aggregates that function as a scaffold for inflammasome activation. Cold exposure promoted inflammasome assembly and subsequent IL-1β release triggered by mutated NLRP3. While K⁺ efflux was dispensable, Ca²⁺ was necessary for mutated NLRP3-mediated inflammasome assembly. Notably, Ca²⁺ influx was induc

SUBMITTER: Karasawa T 

PROVIDER: S-EPMC9177154 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature