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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

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, Zu-Xi Yu, Stewart J. Levine, Jay H. Chung

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. More... »

PAGES

6224

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms7224

DOI

http://dx.doi.org/10.1038/ncomms7224

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030827025

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25692509


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