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Diesel exhaust particle induction of IL-17A contributes to severe asthma.
J Allergy Clin Immunol 2013; 132(5):1194-1204.e2JA

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.

Authors+Show Affiliations

Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24060272

Citation

Brandt, Eric B., et al. "Diesel Exhaust Particle Induction of IL-17A Contributes to Severe Asthma." The Journal of Allergy and Clinical Immunology, vol. 132, no. 5, 2013, pp. 1194-1204.e2.
Brandt EB, Kovacic MB, Lee GB, et al. Diesel exhaust particle induction of IL-17A contributes to severe asthma. J Allergy Clin Immunol. 2013;132(5):1194-1204.e2.
Brandt, E. B., Kovacic, M. B., Lee, G. B., Gibson, A. M., Acciani, T. H., Le Cras, T. D., ... Khurana Hershey, G. K. (2013). Diesel exhaust particle induction of IL-17A contributes to severe asthma. The Journal of Allergy and Clinical Immunology, 132(5), pp. 1194-1204.e2. doi:10.1016/j.jaci.2013.06.048.
Brandt EB, et al. Diesel Exhaust Particle Induction of IL-17A Contributes to Severe Asthma. J Allergy Clin Immunol. 2013;132(5):1194-1204.e2. PubMed PMID: 24060272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diesel exhaust particle induction of IL-17A contributes to severe asthma. AU - Brandt,Eric B, AU - Kovacic,Melinda Butsch, AU - Lee,Gerald B, AU - Gibson,Aaron M, AU - Acciani,Thomas H, AU - Le Cras,Timothy D, AU - Ryan,Patrick H, AU - Budelsky,Alison L, AU - Khurana Hershey,Gurjit K, Y1 - 2013/09/20/ PY - 2013/01/14/received PY - 2013/06/24/revised PY - 2013/06/27/accepted PY - 2013/9/25/entrez PY - 2013/9/26/pubmed PY - 2014/1/8/medline KW - AHR KW - Airway hyperresponsiveness KW - Allergic asthma KW - BALF KW - Bronchoalveolar lavage fluid KW - DEP KW - Diesel exhaust particle KW - Forkhead box protein 3 KW - Foxp3 KW - GCPCR KW - Greater Cincinnati Pediatric Clinic Repository KW - HDM KW - House dust mite KW - IL-13 receptor KW - IL-13R KW - IL-17A KW - OR KW - Odds ratio KW - PE KW - PEES KW - Pediatric Environmental Exposures Study KW - Phycoerythrin KW - Regulatory T KW - SPT KW - Skin prick test KW - Treg KW - diesel exhaust particle KW - house dust mite KW - regulatory T cell SP - 1194 EP - 1204.e2 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 132 IS - 5 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/24060272/Diesel_exhaust_particle_induction_of_IL_17A_contributes_to_severe_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(13)01208-6 DB - PRIME DP - Unbound Medicine ER -