Publication Date:
2018-09-19
Description:
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+sensor and does not associate with NLRP3 under conditions stimulating exclusively Cl−efflux, but does after K+efflux, activating the complex driving inflammation. Our investigation delivers mechanistic understanding into inflammasome activation and the regulation of inflammatory responses.
Print ISSN:
0027-8424
Electronic ISSN:
1091-6490
Topics:
Biology
,
Medicine
,
Natural Sciences in General
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