IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma.
J Immunol
; 181(9): 6117-24, 2008 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-18941201
ABSTRACT
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Macrófagos Alveolares
/
Interleucina-17
/
Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Female
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article