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

Published:September 23, 2013DOI:


      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.


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


      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.


      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 TH2 and TH17 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.


      Expansion of TH17 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.

      Key words

      Abbreviations used:

      AHR (Airway hyperresponsiveness), BALF (Bronchoalveolar lavage fluid), DEP (Diesel exhaust particle), Foxp3 (Forkhead box protein 3), GCPCR (Greater Cincinnati Pediatric Clinic Repository), HDM (House dust mite), IL-13R (IL-13 receptor), OR (Odds ratio), PE (Phycoerythrin), PEES (Pediatric Environmental Exposures Study), SPT (Skin prick test), Treg (Regulatory T)
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      Linked Article

      • DEP-induced TH17 response in asthmatic subjects
        Journal of Allergy and Clinical ImmunologyVol. 133Issue 5
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          We read with great interest the recent study by Brandt et al1 about the key role of IL-17A and its producers such as TH17 cells in diesel exhaust particle (DEP)-mediated severe allergic asthma. Although we appreciate their comprehensive work, we have few comments and queries for the article. (1) We feel as if there is something a little off with the involvement of IL-6 as a proinflammatory cytokine because its precise role in inflammation remains controversial. Qiu et al2 have reported that IL-6 knockout (−/−) mice revealed enhanced airway inflammation after chronic exposure to aeroantigen as compared with wild-type (WT) littermates, implying its antiinflammatory potential.
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