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MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1

dc.contributor.authorSchmolka, Nina
dc.contributor.authorPapotto, Pedro H.
dc.contributor.authorRomero, Paula Vargas
dc.contributor.authorAmado, Tiago
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorAmorim, Ana
dc.contributor.authorRodrigues, Ana F.
dc.contributor.authorGordon, Katrina E.
dc.contributor.authorCoroadinha, Ana S.
dc.contributor.authorBoldin, Mark
dc.contributor.authorSerre, Karine
dc.contributor.authorBuck, Amy H.
dc.contributor.authorGomes, Anita Quintal
dc.contributor.authorSilva-Santos, Bruno
dc.date.accessioned2018-06-11T16:03:10Z
dc.date.available2018-06-11T16:03:10Z
dc.date.issued2018-05
dc.description.abstractγδ T cells are major providers of proinflammatory cytokines. They are preprogrammed in the mouse thymus into distinct subsets producing either interleukin-17 (IL-17) or interferon-γ (IFN-γ), which segregate with CD27 expression. In the periphery, CD27- γδ (γδ27-) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-γ; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in γδ T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-γ expression in γδ27- T cells in vitro and in vivo. On the basis of biochemical purification of Argonaute 2-bound miR-146a targets, we identified Nod1 to be a relevant mRNA target that regulates γδ T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17+ IFN-γ+ γδ27- cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of γδ T cell effector functions and plasticity.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSchmolka N, Papotto PH, Romero PV, Amado T, Enguita FJ, Gomes AQ, et al. MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1. Sci Immunol. 2018;3(23).pt_PT
dc.identifier.doi10.1126/sciimmunol.aao1392pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/8618
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSciencept_PT
dc.relation.publisherversionhttp://immunology.sciencemag.org/content/3/23/eaao1392.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectT cellspt_PT
dc.subjectProinflammatory cytokinespt_PT
dc.subjectPTDC/BEX-BCM/3592/2014pt_PT
dc.titleMicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBEX-BCM%2F3592%2F2014/PT
oaire.citation.issue23pt_PT
oaire.citation.startPageeaao1392pt_PT
oaire.citation.titleScience Immunologypt_PT
oaire.citation.volume3pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication70eddb2f-fa08-408b-8ac9-a2db43a95b39
relation.isProjectOfPublication.latestForDiscovery70eddb2f-fa08-408b-8ac9-a2db43a95b39

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