The Journal of Immunology, 2008, 181, 6117 -6124
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Chuanwang Song^2,*, Liqiong Luo^2,*, Zhang Lei^*, Bo Li^*, Zhihui Liang, Guanghui Liu, Dong Li^*, Guimei Zhang^*, Bo Huang^3,* and Zuo-Hua Feng^3,*

^* Department of Biochemistry & Molecular Biology, Department of Immunology, Tongji Medical College, and Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People’s Republic of China

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.

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¹ The work was supported by the National Natural Science Foundation of China (No. 30771974 and No. 30772589).

² C.S. and L.L. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Bo Huang or Professor Zuo-Hua Feng, Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People’s Republic of China. E-mail addresses: tjhuangbo@hotmail.com or fengzhg@public.wh.hb.cn

⁴ Abbreviations used in this paper: BALF, bronchoalveolar lavage fluid; BAL, bronchoalveolar lavage; 2-CA, 2-chloroadenosine; DC, dendritic cell; AM, alveolar macrophage; IM, interstitial macrophage; PM, peritoneal macrophage.