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Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase

Author

Listed:
  • Amarjit Mishra

    (Laboratory of Asthma and Lung Inflammation, NHLBI, NIH)

  • Alexandra L. Brown

    (Laboratory of Obesity and Aging Research, NHLBI, NIH)

  • Xianglan Yao

    (Laboratory of Asthma and Lung Inflammation, NHLBI, NIH)

  • Shutong Yang

    (Laboratory of Obesity and Aging Research, NHLBI, NIH)

  • Sung-Jun Park

    (Laboratory of Obesity and Aging Research, NHLBI, NIH)

  • Chengyu Liu

    (Transgenic Core Facility, NHLBI, NIH)

  • Pradeep K. Dagur

    (Flow Cytometry Core Facility, NHLBI, NIH)

  • J. Philip McCoy

    (Flow Cytometry Core Facility, NHLBI, NIH)

  • Karen J. Keeran

    (Animal Surgery and Resources Core Facility, NHLBI, NIH)

  • Gayle Z. Nugent

    (Animal Surgery and Resources Core Facility, NHLBI, NIH)

  • Kenneth R. Jeffries

    (Animal Surgery and Resources Core Facility, NHLBI, NIH)

  • Xuan Qu

    (Pathology Core Facility, NHLBI, NIH)

  • Zu-Xi Yu

    (Pathology Core Facility, NHLBI, NIH)

  • Stewart J. Levine

    (Laboratory of Asthma and Lung Inflammation, NHLBI, NIH)

  • Jay H. Chung

    (Laboratory of Obesity and Aging Research, NHLBI, NIH)

Abstract

DNA-dependent protein kinase (DNA-PK) mediates double-stranded DNA break repair, V(D)J recombination and immunoglobulin class switch recombination, as well as innate immune and pro-inflammatory responses. However, there is limited information regarding the role of DNA-PK in adaptive immunity mediated by dendritic cells (DCs), which are the primary antigen-presenting cells in allergic asthma. Here we show that house dust mite induces DNA-PK phosphorylation, which is a marker of DNA-PK activation, in DCs via the generation of intracellular reactive oxygen species. We also demonstrate that pharmacological inhibition of DNA-PK, as well as the specific deletion of DNA-PK in DCs, attenuates the induction of allergic sensitization and Th2 immunity via a mechanism that involves the impaired presentation of mite antigens. Furthermore, pharmacological inhibition of DNA-PK following antigen priming similarly reduces the manifestations of mite-induced airway disease. Collectively, these findings suggest that DNA-PK may be a potential target for treatment of allergic asthma.

Suggested Citation

  • Amarjit Mishra & Alexandra L. Brown & Xianglan Yao & Shutong Yang & Sung-Jun Park & Chengyu Liu & Pradeep K. Dagur & J. Philip McCoy & Karen J. Keeran & Gayle Z. Nugent & Kenneth R. Jeffries & Xuan Qu, 2015. "Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase," Nature Communications, Nature, vol. 6(1), pages 1-18, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7224
    DOI: 10.1038/ncomms7224
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