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dc.contributor.authorArbore, Giuseppina
dc.contributor.authorWest, Erin
dc.contributor.authorRahman, Jubayer
dc.contributor.authorLe Friec, Gaelle
dc.contributor.authorNiyonzima, Nathalie
dc.contributor.authorMehdi, Pirooznia
dc.contributor.authorIlker, Tunc
dc.contributor.authorPolychronis, Pavlidis
dc.contributor.authorNicholas, Powell
dc.contributor.authorLi, Yuesheng
dc.contributor.authorLiu, Poching
dc.contributor.authorServais, Aude
dc.contributor.authorCouzi, Lionel
dc.contributor.authorFremeaux-Bacchi, Veronique
dc.contributor.authorPlacais, Leo
dc.contributor.authorFerraro, Alastair
dc.contributor.authorWalsh, Patrick R.
dc.contributor.authorKavanagh, David
dc.contributor.authorAfzali, Behdad
dc.contributor.authorLavender, Paul
dc.contributor.authorLachmann, Helen J.
dc.contributor.authorKemper, Claudia
dc.date.accessioned2019-04-12T07:47:14Z
dc.date.available2019-04-12T07:47:14Z
dc.date.created2018-11-14T00:42:38Z
dc.date.issued2018
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11250/2594386
dc.description.abstractThe induction of human CD4+ Th1 cells requires autocrine stimulation of the complement receptor CD46 in direct crosstalk with a CD4+ T cell-intrinsic NLRP3 inflammasome. However, it is unclear whether human cytotoxic CD8+ T cell (CTL) responses also rely on an intrinsic complement-inflammasome axis. Here we show, using CTLs from patients with CD46 deficiency or with constitutively-active NLRP3, that CD46 delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis. Surprisingly, although CTLs express NLRP3, a canonical NLRP3 inflammasome is not required for normal human CTL activity, as CTLs from patients with hyperactive NLRP3 activity function normally. These findings establish autocrine complement and CD46 activity as integral components of normal human CTL biology, and, since CD46 is only present in humans, emphasize the divergent roles of innate immune sensors between mice and men.nb_NO
dc.language.isoengnb_NO
dc.publisherNature Researchnb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleComplement receptor CD46 co-stimulates optimal human CD8+ T cell effector function via fatty acid metabolismnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.volume9nb_NO
dc.source.journalNature Communicationsnb_NO
dc.source.issue1nb_NO
dc.identifier.doi10.1038/s41467-018-06706-z
dc.identifier.cristin1630237
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcode© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.nb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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