Pharmaceutical Sciences Faculty Publications

Cutting Edge: Ku70 is a Novel Cytosolic DNA Sensor That Induces Type III Rather Than Type I IFN

Document Type

Article

Publication Date

4-15-2011

Journal Title

Journal of Immunology

ISSN

1550-6606

Volume

186

Issue

8

First Page

4541

Last Page

4545

DOI

10.4049/jimmunol.1003389

PubMed ID

21398614

PubMed Central® ID

PMC3720676

Abstract

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.

Keywords

Antigens, nuclear, blotting, cell line, tumor, cytosol, DNA, mutation, promoter regions, genetic, RNA

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