| Literature DB >> 25327457 |
Sarah Kim1, Jessica Becker2, Matthias Bechheim3, Vera Kaiser3, Mahdad Noursadeghi4, Nadine Fricker2, Esther Beier3, Sven Klaschik5, Peter Boor6, Timo Hess2, Andrea Hofmann2, Stefan Holdenrieder7, Jens R Wendland8, Holger Fröhlich9, Gunther Hartmann7, Markus M Nöthen2, Bertram Müller-Myhsok10, Benno Pütz11, Veit Hornung3, Johannes Schumacher2.
Abstract
Toll-like receptors (TLRs) play a key role in innate immunity. Apart from their function in host defense, dysregulation in TLR signalling can confer risk to autoimmune diseases, septic shock or cancer. Here we report genetic variants and transcripts that are active only during TLR signalling and contribute to interindividual differences in immune response. Comparing unstimulated versus TLR4-stimulated monocytes reveals 1,471 expression quantitative trait loci (eQTLs) that are unique to TLR4 stimulation. Among these we find functional SNPs for the expression of NEU4, CCL14, CBX3 and IRF5 on TLR4 activation. Furthermore, we show that SNPs conferring risk to primary biliary cirrhosis (PBC), inflammatory bowel disease (IBD) and celiac disease are immune response eQTLs for PDGFB and IL18R1. Thus, PDGFB and IL18R1 represent plausible candidates for studying the pathophysiology of these disorders in the context of TLR4 activation. In summary, this study presents novel insights into the genetic basis of the innate immune response and exemplifies the value of eQTL studies in the context of exogenous cell stimulation.Entities:
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Year: 2014 PMID： 25327457 DOI： 10.1038/ncomms6236
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919