Abstract：
BACKGROUND: Diesel engine exhaust (DEE) is associated with the development and exacerbation of asthma. Studies have shown that DEE can aggravate allergen-induced eosinophilic inflammation in lung. However, it remains not clear that whether DEE alone could initiate non-allergic eosinophilic inflammation and airway hyperresponsiveness (AHR) through innate lymphoid cells (ILCs) pathway.
OBJECTIVE: This study aims to investigate the airway inflammation and hyperresponsiveness and its relationship with ILC after DEE exposure.
METHODS: Non-sensitized BALB/c mice were exposed in the chamber of diesel exhaust or filtered air for 2, 4, and 6 weeks (4 h/day, 6 days/week). Anti-CD4 mAb or anti-Thy1.2 mAb was administered by intraperitoneal injection to inhibit CD4+T or ILCs respectively. AHR、airway inflammation and ILCs were assessed.
RESULTS: DEE exposure induced significantly elevated level of neutrophils, eosinophils, collagen content at 4, 6 weeks. Importantly, the airway AHR was only significant in the 4weeks-DEE exposure group. No difference of the functional proportions of Th2 cells was found between exposure group and control group. The proportions of IL-5+ILC2, IL-17+ILC significantly increased in 2, 4weeks-DEE exposure group. After depletion of CD4+T cells, both the proportion of IL-5+ILC2 and IL-17A ILCs was higher in the 4weeks-DEE exposure group which induced AHR, neutrophilic and eosinophilic inflammation accompanied by the IL-5, IL-17A levels.
CONCLUSIONS: Diesel engine exhaust alone can imitate asthmatic characteristics in mice model. Lung-resident ILCs are one of the major effectors cells responsible for a mixed Th2/Th17 response and AHR.
OBJECTIVE: This study aims to investigate the airway inflammation and hyperresponsiveness and its relationship with ILC after DEE exposure.
METHODS: Non-sensitized BALB/c mice were exposed in the chamber of diesel exhaust or filtered air for 2, 4, and 6 weeks (4 h/day, 6 days/week). Anti-CD4 mAb or anti-Thy1.2 mAb was administered by intraperitoneal injection to inhibit CD4+T or ILCs respectively. AHR、airway inflammation and ILCs were assessed.
RESULTS: DEE exposure induced significantly elevated level of neutrophils, eosinophils, collagen content at 4, 6 weeks. Importantly, the airway AHR was only significant in the 4weeks-DEE exposure group. No difference of the functional proportions of Th2 cells was found between exposure group and control group. The proportions of IL-5+ILC2, IL-17+ILC significantly increased in 2, 4weeks-DEE exposure group. After depletion of CD4+T cells, both the proportion of IL-5+ILC2 and IL-17A ILCs was higher in the 4weeks-DEE exposure group which induced AHR, neutrophilic and eosinophilic inflammation accompanied by the IL-5, IL-17A levels.
CONCLUSIONS: Diesel engine exhaust alone can imitate asthmatic characteristics in mice model. Lung-resident ILCs are one of the major effectors cells responsible for a mixed Th2/Th17 response and AHR.
摘要：
背景：柴油发动机废气（DEE）与哮喘的发展和恶化有关。研究表明，DEE可以加重过敏原诱导的肺部嗜酸性粒细胞性炎症。然而,目前尚不清楚单独的DEE是否可以通过先天淋巴细胞(ILC)途径启动非过敏性嗜酸性粒细胞炎症和气道高反应性(AHR).
目的：本研究旨在探讨DEE暴露后气道炎症和高反应性及其与ILC的关系。
方法：将未致敏的BALB/c小鼠暴露于柴油机排气室或过滤空气室中2、4和6周（4小时/天，6天/周）。通过腹膜内注射施用抗CD4mAb或抗Thy1.2mAb以分别抑制CD4+T或ILC。评估AHR、气道炎症和ILC。
结果：DEE暴露导致中性粒细胞水平显著升高，嗜酸性粒细胞,4、6周时的胶原含量。重要的是,气道AHR仅在4周-DEE暴露组中显著.暴露组与对照组之间Th2细胞的功能比例无差异。2、4周-DEE暴露组IL-5+ILC2、IL-17+ILC比例显著增加。CD4+T细胞耗尽后，在诱导AHR的4周-DEE暴露组中，IL-5+ILC2和IL-17AILC的比例均较高，嗜中性粒细胞和嗜酸性粒细胞炎症伴有IL-5，IL-17A水平。
结论：单独的柴油机废气可以模拟小鼠模型的哮喘特征。肺驻留ILC是负责混合Th2/Th17反应和AHR的主要效应细胞之一。
目的：本研究旨在探讨DEE暴露后气道炎症和高反应性及其与ILC的关系。
方法：将未致敏的BALB/c小鼠暴露于柴油机排气室或过滤空气室中2、4和6周（4小时/天，6天/周）。通过腹膜内注射施用抗CD4mAb或抗Thy1.2mAb以分别抑制CD4+T或ILC。评估AHR、气道炎症和ILC。
结果：DEE暴露导致中性粒细胞水平显著升高，嗜酸性粒细胞,4、6周时的胶原含量。重要的是,气道AHR仅在4周-DEE暴露组中显著.暴露组与对照组之间Th2细胞的功能比例无差异。2、4周-DEE暴露组IL-5+ILC2、IL-17+ILC比例显著增加。CD4+T细胞耗尽后，在诱导AHR的4周-DEE暴露组中，IL-5+ILC2和IL-17AILC的比例均较高，嗜中性粒细胞和嗜酸性粒细胞炎症伴有IL-5，IL-17A水平。
结论：单独的柴油机废气可以模拟小鼠模型的哮喘特征。肺驻留ILC是负责混合Th2/Th17反应和AHR的主要效应细胞之一。
