Diesel exhaust particle induction of IL17A contributes to severe asthma (P6373)

Abstract The factors that promote IL17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEP) are a major component of traffic related air pollution and are implicated in asthma exacerbation. We assessed the impact of DEP exposure on asthma severity in asthmatic children from the Greater Cincinnati Pediatric Clinic Repository. Among high DEP-exposed children with allergic asthma, 32.2% of the children had severe asthma, compared to only 14.2% in the low DEP-exposed group. Similarly, Balb/c mice co-exposed to DEP and house dust mite extract (HDM) markedly demonstrated enhanced airway inflammation and hyperresponsiveness (AHR) compared to HDM alone. Exposure to DEP alone did not induce classic features of asthma but generated a Th17 response. DEP and HDM co-exposures enhanced pulmonary Th2 and Th17 cell numbers compared to HDM alone. High DEP-exposed children with allergic asthma had elevated serum IL17A levels compared with low DEP-exposed children. Finally, IL17A neutralization alleviated DEP-induced exacerbation of AHR. In conclusion, Th17 cells contribute to DEP-mediated exacerbation of allergen-induced asthma. Neutralization of IL17A may be a useful therapeutic strategy to counteract the asthma promoting effects of traffic related air pollution especially in severe asthmatics.