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Human naïve regulatory T-cells feature high steady-state turnover and are maintained by IL-7

2016-03-15Journal article Open access
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dc.contributor.authorSilva, Susana L.
dc.contributor.authorAlbuquerque, Adriana S.
dc.contributor.authorSerra-Caetano, Ana
dc.contributor.authorFoxall, Russell B.
dc.contributor.authorPires, Ana R.
dc.contributor.authorMatoso, Paula
dc.contributor.authorFernandes, Susana M.
dc.contributor.authorFerreira, João
dc.contributor.authorCheynier, Rémi
dc.contributor.authorVictorino, Rui M. M.
dc.contributor.authorCaramalho, Iris
dc.contributor.authorBarata, João T.
dc.contributor.authorSousa, Ana E.
dc.date.accessioned2016-07-18T11:36:01Z
dc.date.available2016-07-18T11:36:01Z
dc.date.issued2016-03-15
dc.description.abstractNaïve FoxP3-expressing regulatory T-cells (Tregs) are essential to control immune responses via continuous replenishment of the activated-Treg pool with thymus-committed suppressor cells. The mechanisms underlying naïve-Treg maintenance throughout life in face of the age-associated thymic involution remain unclear. We found that in adults thymectomized early in infancy the naïve-Treg pool is remarkably well preserved, in contrast to conventional naïve CD4 T-cells. Naïve-Tregs featured high levels of cycling and pro-survival markers, even in healthy individuals, and contrasted with other circulating naïve/memory CD4 T-cell subsets in terms of their strong γc-cytokine-dependent signaling, particularly in response to IL-7. Accordingly, ex-vivo stimulation of naïve-Tregs with IL-7 induced robust cytokine-dependent signaling, Bcl-2 expression, and phosphatidylinositol 3-kinase (PI3K)-dependent proliferation, whilst preserving naïve phenotype and suppressive capacity. Altogether, our data strongly implicate IL-7 in the thymus-independent long-term survival of functional naïve-Tregs, and highlight the potential of targeting the IL-7 pathway to modulate Tregs in different clinical settings.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (FCT; POCI2010/IC/83068/2007 to RMMV; PTDC/SAU-MIC/109786/2009 to AES), and Gulbenkian Foundation (96526/2009 to JF; P132532/2013 to AES). SLS, ASA, RBF, ARP, PM and SMF received FCT scholarships.pt_PT
dc.identifier.citationOncotarget, Vol. 7, No. 11pt_PT
dc.identifier.doi10.18632/oncotarget.7512pt_PT
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10451/24384
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherImpact Journalspt_PT
dc.relationHIV/AIDS: contribute of naïve CD4 T cell homeostasis
dc.relation.publisherversionhttp://www.impactjournals.com/oncotarget/pt_PT
dc.subjectIL-7pt_PT
dc.subjectImmune responsept_PT
dc.subjectHuman regulatory T-cellspt_PT
dc.subjectNaïve regulatory T-cellspt_PT
dc.subjectRegulatory T-cell homeostasispt_PT
dc.subjectThymectomypt_PT
dc.titleHuman naïve regulatory T-cells feature high steady-state turnover and are maintained by IL-7pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleHIV/AIDS: contribute of naïve CD4 T cell homeostasis
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-MIC%2F109786%2F2009/PT
oaire.citation.titleOncotargetpt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationf1e55a56-8dfd-400d-a4d0-9b655f2e66b3
relation.isProjectOfPublication.latestForDiscoveryf1e55a56-8dfd-400d-a4d0-9b655f2e66b3

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