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

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.
TypeArticle
URIhttp://hdl.handle.net/1822/18618
DOI10.1371/journal.pone.0028256
ISSN1932-6203
Publisher versionhttp://dx.doi.org/10.1371/journal.pone.0028256
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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