| First Author | Green JP | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 40 | Pages | E9371-E9380 |
| PubMed ID | 30232264 | Mgi Jnum | J:266649 |
| Mgi Id | MGI:6201641 | Doi | 10.1073/pnas.1812744115 |
| Citation | Green JP, et al. (2018) Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. Proc Natl Acad Sci U S A 115(40):E9371-E9380 |
| abstractText | 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-1beta (IL-1beta). 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-1beta 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. |
