Dendritic cells and alveolar macrophages mediate IL-13-induced airway inflammation and chemokine production

详细信息	查看全文 | 推荐本文 |

• 作者：Margaret Crapster-Pregont ; BS ; Janice Yeo ; BS ; Raquel L. Sanchez ; BS ; Douglas A. Kuperman ; PhD ; ^{d-kuperman@northwestern.edu}
• 关键词：Asthma ; airway ; macrophage ; chemokines ; inflammation ; IL-13 ; IFN-纬 ; CD11b ; dendritic cell ; macrophage-derived chemokine ; thymus and activation-regulated chemokine
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：June, 2012
• 卷：129
• 期：6
• 页码：1621-1627.e3
• 文件大小：722 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Background

IL-13 in the airway induces pathologies that are highly characteristic of asthma, including mucus metaplasia, airway hyperreactivity (AHR), and airway inflammation. As such, it is important to identify the IL-13-responding cell types that mediate each of the above pathologies. For example, IL-13鈥檚 effects on epithelium contribute to mucus metaplasia and AHR. IL-13鈥檚 effects on smooth muscle also contribute to AHR. However, it has been difficult to identify the cell types that mediate IL-13-induced airway inflammation.

Objective

We sought to determine which cell types mediate IL-13-induced airway inflammation.

Methods

We treated the airways of mice with IL-13 alone or in combination with IFN-纬. We associated the inhibitory effect of IFN-纬 on IL-13-induced airway inflammation and chemokine production with cell types in the lung that coexpress IL-13 and IFN-纬 receptors. We then evaluated IL-13-induced responses in CD11c promoter-directed diphtheria toxin receptor-expressing mice that were depleted of both dendritic cells and alveolar macrophages and in CD11b promoter-directed diphtheria toxin receptor-expressing mice that were depleted of dendritic cells.

Results

Dendritic cell and alveolar macrophage depletion protected mice from IL-13-induced airway inflammation and CCL11, CCL24, CCL22, and CCL17 chemokine production. Preferential depletion of dendritic cells protected mice from IL-13-induced airway inflammation and CCL22 and CCL17 chemokine production but not from IL-13-induced CCL11 and CCL24 chemokine production. In either case mice were not protected from IL-13-induced AHR and mucus metaplasia.

Conclusions

Pulmonary dendritic cells and alveolar macrophages mediate IL-13-induced airway inflammation and chemokine production.