The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation
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 s...
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Published in | PloS one Vol. 6; no. 11; p. e28256 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
23.11.2011
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Conceived and designed the experiments: AC MS PL JP LP FA LR AGC FR. Performed the experiments: AC NSO MS CC AJA MTC. Analyzed the data: AC NSO MS CC AJA MTC PL JP LP FA LR AGC FR. Contributed reagents/materials/analysis tools: AGC FR. Wrote the paper: AC NSO MS CC AJA MTC PL JP LP FA LR AGC FR. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0028256 |