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Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming

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dc.contributor.authorMartín Sánchez, María Rosario Fátima
dc.contributor.authorPelegrín Vivancos, Pablo
dc.contributor.authorGreen, Jack Peter
dc.contributor.authorYu, Shi
dc.contributor.authorLopez-Castejon, Gloria
dc.contributor.authorLawrence, Catherine B.
dc.contributor.authorBrough, David
dc.contributor.departmentFarmacología
dc.date.accessioned2026-02-20T12:30:31Z
dc.date.available2026-02-20T12:30:31Z
dc.date.issued2018-09-19
dc.description.abstractThe NLRP3 inflammasome is an important regulator of inflammation and immunity. It is a multi-molecular platform formed within cells that facilitates the activation of pro-inflammatory caspases to drive secretion of cytokines such as 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, though 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 new mechanistic understanding into inflammasome activation and the regulation of inflammatory responses.
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dc.format.extent10
dc.identifier.citationGreen, J., Yu, S., Martín-Sánchez, F., Pelegrin, P., Lopez-Castejon, G., Lawrence, C. B., & Brough, D. (2018). Chloride regulates dynamic NLRP3-dependent ASC oligomerisation and inflammasome priming. Proceedings of the National Academy of Sciences, 115(40), E9371-E9380. https://doi.org/10.1073/pnas.1812744115
dc.identifier.doihttps://doi.org/10.1073/pnas.1812744115
dc.identifier.issn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/10201/209361
dc.languageeng
dc.publisherNational Academy of Sciences
dc.relationEste trabajo ha sido financiado por Wellcome Trust and the Royal Society (Reino Unido) (104192/Z/14/Z), Medical Research Council (MR/N029992/1) y European Research Council (ERC-2013-CoG Grant red 614578)
dc.relation.publisherversionhttps://www.pnas.org/doi/10.1073/pnas.1812744115
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectInflammation
dc.subjectCaspase-1
dc.subjectInterleukin-1
dc.subjectChloride
dc.subjectInflammasome
dc.subject.odsObjetivo 3: Salud
dc.titleChloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublicationeefc2e40-b110-47b5-a081-bcf37256af4c
relation.isAuthorOfPublication547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
relation.isAuthorOfPublication.latestForDiscoveryeefc2e40-b110-47b5-a081-bcf37256af4c
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