title: Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN.
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.
authors.affiliation: Applied and Developmental Research Directorate, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Terrence W
authors.initials: TW
authors.lastname: Brann
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Raphael M
authors.initials: RM
authors.lastname: Oguariri
authors.forename: Kristy B
authors.initials: KB
authors.lastname: Lidie
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamichi
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Huang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Michael W
authors.initials: MW
authors.lastname: Baseler
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Imamichi
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D000072200:Ku Autoantigen; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000095022:Interferon Lambda
chemical_list: D034961:Antigens, Nuclear; D004247:DNA; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D007372:Interferons; D007378:Interleukins; D000072200:Ku Autoantigen; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse