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

  1. Author:
    Zhang, X.
    Brann, T. W.
    Zhou, M.
    Yang, J.
    Oguariri, R. M.
    Lidie, K. B.
    Imamichi, H.
    Huang, D. W.
    Lempicki, R. A.
    Baseler, M. W.
    Veenstra, T. D.
    Young, H. A.
    Lane, H. C.
    Imamichi, T.

  2. Author Address

    [Imamichi, Tomozumi] NCI, Appl & Dev Res Directorate, Lab Human Retrovirol, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Zhou, Ming; Veenstra, Timothy D.] NCI, Adv Technol Program Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Imamichi, Hiromi; Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Young, Howard A.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA.;Imamichi, T, NCI, Appl & Dev Res Directorate, Lab Human Retrovirol, Sci Applicat Int Corp Frederick Inc, Bldg 550,Room 126,POB B, Frederick, MD 21702 USA.;timamichi@mail.nih.gov
    1. Year: 2011
    2. Date: Apr
  2. Journal: Journal of Immunology
    1. 186
    2. 8
    3. Pages: 4541-4545
  4. Type of Article: Article
  5. ISSN: 0022-1767
  1. 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-lambda 1) 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-l1 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. The Journal of Immunology, 2011, 186: 4541-4545.

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External Sources

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  2. DOI: 10.4049/jimmunol.1003389
  3. View record in Web of Science®
  4. WOS: 000289081500003

Library Notes

  1. Fiscal Year: FY2010-2011
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