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IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma.

Authors: Song, C  Luo, L  Lei, Z  Li, B  Liang, Z  Liu, G  Li, D  Zhang, G  Huang, B  Feng, ZH 
Citation: Song C, etal., J Immunol. 2008 Nov 1;181(9):6117-24.
Pubmed: (View Article at PubMed) PMID:18941201

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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CRRD Object Information
CRRD ID: 4889152
Created: 2010-11-30
Species: All species
Last Modified: 2010-11-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.