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.
The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation / A.Carvalho; NS.Osório; M.Saraiva; C.Cunha; AJ. Almeida; M. Teixeira-Coelho; P.Ludovico; J. Pedrosa; L. Pitzurra; F. Aversa; L. Romani; AG. Castro; F.Rodrigues. - In: PLOS ONE. - ISSN 1932-6203. - 6(2011), p. e28256.