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IL-17-Producing Alveolar Macrophages Mediate Allergic Lung Inflammation Related to Asthma¹

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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{at}hotmail.com or fengzhg{at}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.

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The JI 2008 181: 5811-5812. [Full Text]