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Diesel exhaust particle induction of IL-17A contributes to severe asthma.


ABSTRACT:

Background

IL-17A has been implicated in severe forms of asthma. However, the factors that promote IL-17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEPs) are a major component of traffic-related air pollution and are implicated in asthma pathogenesis and exacerbation.

Objective

We sought to determine the mechanism by which DEP exposure affects asthma severity using human and mouse studies.

Methods

BALB/c mice were challenged with DEPs with or without house dust mite (HDM) extract. Airway inflammation and function, bronchoalveolar lavage fluid cytokine levels, and flow cytometry of lung T cells were assessed. The effect of DEP exposure on the frequency of asthma symptoms and serum cytokine levels was determined in children with allergic asthma.

Results

In mice exposure to DEPs alone did not induce asthma. DEP and HDM coexposure markedly enhanced airway hyperresponsiveness compared with HDM exposure alone and generated a mixed T(H)2 and T(H)17 response, including IL-13(+)IL-17A(+) double-producing T cells. IL-17A neutralization prevented DEP-induced exacerbation of airway hyperresponsiveness. Among 235 high DEP-exposed children with allergic asthma, 32.2% had more frequent asthma symptoms over a 12-month period compared with only 14.2% in the low DEP-exposed group (P = .002). Additionally, high DEP-exposed children with allergic asthma had nearly 6 times higher serum IL-17A levels compared with low DEP-exposed children.

Conclusions

Expansion of T(H)17 cells contributes to DEP-mediated exacerbation of allergic asthma. Neutralization of IL-17A might be a useful potential therapeutic strategy to counteract the asthma-promoting effects of traffic-related air pollution, especially in highly exposed patients with severe allergic asthma.

SUBMITTER: Brandt EB 

PROVIDER: S-EPMC3845500 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Diesel exhaust particle induction of IL-17A contributes to severe asthma.

Brandt Eric B EB   Kovacic Melinda Butsch MB   Lee Gerald B GB   Gibson Aaron M AM   Acciani Thomas H TH   Le Cras Timothy D TD   Ryan Patrick H PH   Budelsky Alison L AL   Khurana Hershey Gurjit K GK  

The Journal of allergy and clinical immunology 20130920 5


<h4>Background</h4>IL-17A has been implicated in severe forms of asthma. However, the factors that promote IL-17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEPs) are a major component of traffic-related air pollution and are implicated in asthma pathogenesis and exacerbation.<h4>Objective</h4>We sought to determine the mechanism by which DEP exposure affects asthma severity using human and mouse studies.<h4>Methods</h4>BALB/c mice were challe  ...[more]

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