The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 an...

• 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
• Date: 2011
• Persistent ID: http://hdl.handle.net/1822/18618
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): Allelic variants; Toll-like receptors (TLRs); Human TLR9 promoter; rs5743836 polymorphism; IL-6-responding element; B-cell proliferation; TLR9 agonists; TLR9 antagonists
• Document Type: Article
• Language: English

Description

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.