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

Authors: Brandt, Eric B; Kovacic, Melinda Butsch; Lee, Gerald B; Gibson, Aaron M; Acciani, Thomas H; Le Cras, Timothy D; Ryan, Patrick H; Budelsky, Alison L; Khurana Hershey, Gurjit K

Published In J Allergy Clin Immunol, (2013 Nov)

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.

PubMed ID: 24060272 Exiting the NIEHS site

MeSH Terms: Adolescent; Allergens/immunology; Animals; Asthma/etiology*; Child; Child, Preschool; Cytokines/biosynthesis; Cytokines/blood; Disease Models, Animal; Female; Humans; Hyaluronan Receptors/metabolism; Inflammation/etiology; Inhalation Exposure/adverse effects; Interleukin-17/biosynthesis*; Interleukin-17/blood; L-Selectin/metabolism; Lung/immunology; Lung/metabolism; Male; Mice; Pyroglyphidae/immunology; Respiratory Hypersensitivity/etiology; Th17 Cells/immunology; Th17 Cells/metabolism; Th2 Cells/immunology; Th2 Cells/metabolism; Vehicle Emissions*/toxicity

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Last Reviewed: October 07, 2024