IL-17-Producing Alveolar Macrophages Mediate Allergic Lung Inflammation Related to Asthma

被引:241
作者
Song, Chuanwang [1 ]
Luo, Liqiong [1 ]
Lei, Zhang [1 ]
Li, Bo [1 ]
Liang, Zhihui [2 ]
Liu, Guanghui [3 ]
Li, Dong [1 ]
Zhang, Guimei [1 ]
Huang, Bo [1 ]
Feng, Zuo-Hua [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430074, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Wuhan 430074, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Allergy, Wuhan 430074, Peoples R China
关键词
D O I
10.4049/jimmunol.181.9.6117
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-17 is a pivotal proinflammatory molecule in asthmatics. However, the cellular source of IL-17 in asthma has not been identified to date. In this study, we report that macrophages rather than Th17 cells are the main producer of IL-17 in allergic inflammation related to asthma. After OVA challenge in a mouse model mimicking allergic asthma, the increased IL-17(+) cells in the lung were mainly CD11b(+)F4/80(+) macrophages, instead of T cells or others. Importantly, IL-17(+) alveolar macrophages (AMs), but not IL-17(+) interstitial macrophages, were significantly increased after allergen challenge. The increase of IL-17(+) AMs was not due to the influx of IL-17(+) macrophages from circulation or other tissues, but ascribed to the activation of AMs by mediator(s) secreted by IgE/OVA-activated mast cells. Depleting alveolar macrophages or neutralizing IL-17 prevented the initiation of OVA-induced asthma-related inflammation by inhibiting the increase of inflammatory cells and inflammatory factors in bronchoalveolar lavage fluid. Th2 cytokine IL-10 could down-regulate IL-17 expression in alveolar macrophages. The increased IL-17 and the decreased IL-10 in bronchoalveolar lavage fluid were further confirmed in asthmatic patients. These findings suggest that IL-17 is mainly produced by macrophages but not Th17 cells in allergic inflammation related to asthma. Mast cell-released mediators up-regulate the expression of IL-17 by macrophages, whereas IL-10 down-regulates IL-17 expression. The Journal of Immunology, 2008,181: 6117-6124.
引用
收藏
页码:6117 / 6124
页数:8
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