The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation

• Autor(a) principal: Carvalho, Agostinho
• Data de Publicação: 2011
• Outros Autores: 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
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/18618
• topic: Allelic variants; Toll-like receptors (TLRs); Human TLR9 promoter; rs5743836 polymorphism; IL-6-responding element; B-cell proliferation; TLR9 agonists; TLR9 antagonists; Science & Technology

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.