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

Abstract

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's effects on epithelium contribute to mucus metaplasia and AHR. IL-13's 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. We sought to determine which cell types mediate IL-13-induced airway inflammation. We treated the airways of mice with IL-13 alone or in combination with IFN-γ. We associated the inhibitory effect of IFN-γ on IL-13-induced airway inflammation and chemokine production with cell types in the lung that coexpress IL-13 and IFN-γ 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. 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. Pulmonary dendritic cells and alveolar macrophages mediate IL-13-induced airway inflammation and chemokine production.