DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA

Wen Ming Chu, Xing Gong, Zhi Wei Li, Kenji Takabayashi, Hong Hai Ouyang, Yi Chen, Augusto Lois, David J. Chen, Gloria C. Li, Michael Karin, Eyal Raz

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Bacterial DNA and related synthetic immunostimulatory oligodeoxyribonucleotides (ISS-ODN) stimulate innate immunity. However, the molecular recognition mechanism that initiates signaling in response to bacterial DNA and ISS-ODN has not been identified. Herein, we demonstrate that administration of bacterial DNA and ISS-ODN to mice lacking the catalytic subunit of DNA-PK (DNA-PKcs) and in vitro stimulation of BMDM from these mice result in defective induction of IL-6 and IL-12. Further analysis using BMDM of IKKβ(-/-) revealed that both DNA-PKcs and IKKβ are essential for normal cytokine production in response to ISS-ODN or bacterial DNA. ISS-ODN and bacterial DNA activate DNA-PK, which in turn contributes to activation of IKK and NF-κB. These results reveal a novel role of DNA-PKcs in innate immune responses and a link between DNA repair and innate immunity.

Original languageEnglish (US)
Pages (from-to)909-918
Number of pages10
JournalCell
Volume103
Issue number6
StatePublished - 2000

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Chu, W. M., Gong, X., Li, Z. W., Takabayashi, K., Ouyang, H. H., Chen, Y., Lois, A., Chen, D. J., Li, G. C., Karin, M., & Raz, E. (2000). DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA. Cell, 103(6), 909-918.