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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.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.publisherPublic Library of Sciencepor
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
oaire.citationTitlePLoS Onepor
dc.subject.wosScience & Technologypor
sdum.journalPLoS ONEpor
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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