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J Immunol. 2011 Apr 15;186(8):4541-5. doi: 10.4049/jimmunol.1003389. Epub 2011 Mar 11.

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

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Applied and Developmental Research Directorate, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA.


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-λ1) 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-λ1 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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