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Publication : Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN.

First Author  Zhang X Year  2011
Journal  J Immunol Volume  186
Issue  8 Pages  4541-5
PubMed ID  21398614 Mgi Jnum  J:172454
Mgi Id  MGI:5007857 Doi  10.4049/jimmunol.1003389
Citation  Zhang X, et al. (2011) Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN. J Immunol 186(8):4541-5
abstractText  Cytosolic foreign DNA is detected by pattern recognition receptors and mainly induces type I IFN production. We found that transfection of different types of DNA into various untreated cells induces type III IFN (IFN-lambda1) rather than type I IFN, indicating the presence of uncharacterized DNA sensor(s). A pull-down assay using cytosolic proteins identified that Ku70 and Ku80 are the DNA-binding proteins. The knockdown studies and the reporter assay revealed that Ku70 is a novel DNA sensor inducing the IFN-lambda1 activation. The functional analysis of IFNL1 promoter revealed that positive-regulatory domain I and IFN-stimulated response element sites are predominantly involved in the DNA-mediated IFNL1 activation. A pull-down assay using nuclear proteins demonstrated that the IFN-lambda1 induction is associated with the activation of IFN regulatory factor-1 and -7. Thus, to our knowledge, we show for the first time that Ku70 mediates type III IFN induction by DNA.
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