Please use this identifier to cite or link to this item:

TitleThe C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation
Author(s)Carvalho, Agostinho
Osório, Nuno S.
Saraiva, Margarida
Cunha, Cristina
Almeida, A. J.
Coelho, Maria Teixeira
Ludovico, Paula
Pedrosa, Jorge
Pitzurra, Lucia
Aversa, Franco
Romani, Luigina
Castro, António G.
Rodrigues, Fernando José dos Santos
KeywordsAllelic variants
Toll-like receptors (TLRs)
Human TLR9 promoter
rs5743836 polymorphism
IL-6-responding element
B-cell proliferation
TLR9 agonists
TLR9 antagonists
Issue dateNov-2011
PublisherPublic Library of Science
JournalPLoS ONE
Abstract(s)In 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.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
Carvalho A_PLoS One 2011.pdfDocumento principal378,08 kBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID