Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming.

ABSTRACT: The NLRP3 inflammasome is an important regulator of inflammation and immunity. It is a multimolecular platform formed within cells that facilitates the activation of proinflammatory caspases to drive secretion of cytokines such as interleukin-1β (IL-1β). Knowledge of the mechanisms regulating formation of the NLRP3 inflammasome is incomplete. Here we report Cl^- channel-dependent formation of dynamic ASC oligomers and inflammasome specks that remain inactive in the absence of K⁺ efflux. Formed after Cl^- efflux exclusively, ASC specks are NLRP3 dependent, reversible, and inactive, although they further prime inflammatory responses, accelerating and enhancing release of IL-1β in response to a K⁺ efflux-inducing stimulus. NEK7 is a specific K^+</

SUBMITTER: Green JP 

PROVIDER: S-EPMC6176575 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature