Diesel exhaust particle induction of IL-17A contributes to severe asthma.
Diesel exhaust particle induction of IL-17A contributes to severe asthma.
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DOI：
10.1016/j.jaci.2013.06.048
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发表时间：
2013-11
影响因子：
14.2
通讯作者：
Hershey, Gurjit K. Khurana
中科院分区：
文献类型：
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作者：
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.;Hershey, Gurjit K. Khurana
IL-17A与严重形式的哮喘有关。然而，在严重哮喘发病过程中促进IL-17A产生的因素仍不清楚。柴油废气颗粒（DEP）是交通相关空气污染的主要组成部分，与哮喘的发病和加重有关。通过人类和小鼠研究确定DEP暴露影响哮喘严重程度的机制。用DEP +/−屋尘螨提取物（HDM）攻毒Balb/c小鼠。评估气道炎症和功能、BALF细胞因子水平和肺T细胞流式细胞术。在过敏性哮喘患儿中测定DEP暴露对哮喘症状频率和血清细胞因子水平的影响。在小鼠中，单独暴露于DEP不会诱发哮喘。与单独暴露HDM相比，DEP和HDM共暴露可显著提高AHR，并产生混合Th2和Th17反应，包括IL-13+IL-17A+双产t细胞。IL-17A中和可防止深度诱发的AHR恶化。在235名高剂量暴露的过敏性哮喘儿童中，32.2%的儿童在12个月内出现了更频繁的哮喘症状，而低剂量暴露组只有14.2% （p=0.002）。此外，与低暴露儿童相比，高暴露儿童患有过敏性哮喘的血清IL-17A水平高出近6倍。Th17细胞的扩增有助于depp介导的过敏性哮喘加重。IL-17A的中和可能是一种有用的潜在治疗策略，可以抵消交通相关空气污染对哮喘的促进作用，特别是在高度暴露的严重过敏性哮喘患者中。
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 (DEP) are a major component of traffic related air pollution and are implicated in asthma pathogenesis and exacerbation. To determine the mechanism by which DEP exposure impacts asthma severity using human and mouse studies. Balb/c mice were challenged with DEP +/− house dust mite extract (HDM). Airway inflammation and function, BALF cytokine levels, and flow cytometry of lung T cells were assessed. The impact of DEP exposure on frequency of asthma symptoms and serum cytokine levels was determined in children with allergic asthma. In mice, exposure to DEP alone did not induce asthma. DEP and HDM co-exposure markedly enhanced AHR compared to HDM 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 AHR. Among 235 high DEP-exposed children with allergic asthma, 32.2% had more frequent asthma symptoms over a 12 month period, compared to only 14.2% in the low DEP-exposed group (p=0.002). Additionally, high DEP-exposed children with allergic asthma had nearly six 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 may be a useful potential therapeutic strategy to counteract the asthma promoting effects of traffic related air pollution especially in highly exposed severe allergic asthmatics.
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影响因子：
30.5
作者：
通讯作者：
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DOI：
10.1186/1476-069x-8-17
发表时间：
2009-04-16
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Bråbäck L;Forsberg B
通讯作者：
Forsberg B
影响因子：
14.2
作者：
Cosmi, Lorenzo;Maggi, Laura;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
10.4
作者：
Clougherty JE;Levy JI;Kubzansky LD;Ryan PB;Suglia SF;Canner MJ;Wright RJ
通讯作者：
Wright RJ
DOI：
10.1038/nri2870
发表时间：
2010-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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