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

Autor:	Mishra A; Laboratory of Asthma and Lung Inflammation, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Brown AL; Laboratory of Obesity and Aging Research, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Yao X; Laboratory of Asthma and Lung Inflammation, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Yang S; Laboratory of Obesity and Aging Research, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Park SJ; Laboratory of Obesity and Aging Research, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Liu C; Transgenic Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Dagur PK; Flow Cytometry Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., McCoy JP; Flow Cytometry Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Keeran KJ; Animal Surgery and Resources Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Nugent GZ; Animal Surgery and Resources Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Jeffries KR; Animal Surgery and Resources Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Qu X; Pathology Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Yu ZX; Pathology Core Facility, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Levine SJ; Laboratory of Asthma and Lung Inflammation, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA., Chung JH; Laboratory of Obesity and Aging Research, Division of Intramural Research, NHLBI, NIH, Bethesda, Maryland 20892, USA.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2015 Feb 18; Vol. 6, pp. 6224. Date of Electronic Publication: 2015 Feb 18.
DOI:	10.1038/ncomms7224
Abstrakt:	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.
Databáze:	MEDLINE
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