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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:132

Article

Brandt, Eric B.¹  Kovacic, Melinda Butsch¹  Lee, Gerald B.¹  Gibson, Aaron M.¹  Acciani, Thomas H.²  Le Cras, Timothy D.²  Ryan, Patrick H.³  Budelsky, Alison L.⁴  Hershey, Gurjit K. Khurana¹ 

[1] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Div Asthma Res, Cincinnati, OH 45221 USA

[2] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH 45221 USA

[3] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Div Epidemiol & Biostat, Cincinnati, OH 45221 USA

[4] Amgen Inc, Dept Inflammat Res, Seattle, WA USA

关键词: Allergic asthma;    house dust mite;    diesel exhaust particle;    IL-17A;    regulatory T cell;   

DOI  :  10.1016/j.jaci.2013.06.048

来源: Elsevier

【 摘 要 】

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.

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