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; Osório, N. S.; M., Saraiva; C., Cunha; Almeida, A. J.; M., Teixeira Coelho; P., Ludovico; J., Pedrosa; L., Pitzurra; Aversa, Franco; L., Romani; Castro, A. G.; F., Rodrigues. - In: PLOS ONE. - ISSN 1932-6203. - 6:(2011), p. e28256.

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

AVERSA, Franco;
2011-01-01

Abstract

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.
2011
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; Osório, N. S.; M., Saraiva; C., Cunha; Almeida, A. J.; M., Teixeira Coelho; P., Ludovico; J., Pedrosa; L., Pitzurra; Aversa, Franco; L., Romani; Castro, A. G.; F., Rodrigues. - In: PLOS ONE. - ISSN 1932-6203. - 6:(2011), p. e28256.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2438521
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