Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/18618

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dc.contributor.authorCarvalho, Agostinho-
dc.contributor.authorOsório, Nuno S.-
dc.contributor.authorSaraiva, Margarida-
dc.contributor.authorCunha, Cristina-
dc.contributor.authorAlmeida, A. J.-
dc.contributor.authorCoelho, Maria Teixeira-
dc.contributor.authorLudovico, Paula-
dc.contributor.authorPedrosa, Jorge-
dc.contributor.authorPitzurra, Lucia-
dc.contributor.authorAversa, Franco-
dc.contributor.authorRomani, Luigina-
dc.contributor.authorCastro, António G.-
dc.contributor.authorRodrigues, Fernando José dos Santos-
dc.date.accessioned2012-04-13T14:43:21Z-
dc.date.available2012-04-13T14:43:21Z-
dc.date.issued2011-11-
dc.identifier.issn1932-6203por
dc.identifier.urihttp://hdl.handle.net/1822/18618-
dc.description.abstractIn humans, allelic variants in Toll-like receptors (TLRs) associate with several pathologies. However, the underlying cellular and molecular mechanisms of this association remain largely unknown. Analysis of the human TLR9 promoter revealed that the C allele of the rs5743836 polymorphism generates several regulatory sites, including an IL-6-responding element. Here, we show that, in mononuclear cells carrying the TC genotype of rs5743836, IL-6 up-regulates TLR9 expression, leading to exacerbated cellular responses to CpG, including IL-6 production and B-cell proliferation. Our study uncovers a role for the rs5743836 polymorphism in B-cell biology with implications on TLR9-mediated diseases and on the therapeutic usage of TLR9 agonists/antagonists.por
dc.description.sponsorshipFundação para a Ciência e Tecnologia (FCT) This study was supported by FCT - Grant Number PIC/IC/83313/2007.por
dc.language.isoengpor
dc.publisherPublic Library of Sciencepor
dc.rightsopenAccesspor
dc.subjectAllelic variantspor
dc.subjectToll-like receptors (TLRs)por
dc.subjectHuman TLR9 promoterpor
dc.subjectrs5743836 polymorphismpor
dc.subjectIL-6-responding elementpor
dc.subjectB-cell proliferationpor
dc.subjectTLR9 agonistspor
dc.subjectTLR9 antagonistspor
dc.titleThe C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferationpor
dc.typearticlepor
dc.peerreviewedyespor
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0028256por
oaire.citationStartPagee28256por
oaire.citationIssue11por
oaire.citationTitlePLoS Onepor
oaire.citationVolume6por
dc.identifier.doi10.1371/journal.pone.0028256por
dc.identifier.pmid22132241por
dc.subject.wosScience & Technologypor
sdum.journalPLoS ONEpor
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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