In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma
Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell-mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4(+) T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c(+) DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c(+) cells, endogenous or adoptively transferred CD4(+) Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c(+) DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation.
|Adoptive Transfer, Aerosols/administration & dosage, Allergens/administration & dosage/immunology, Animals, Antigens, CD11c/genetics/*immunology, Asthma/chemically induced/genetics/*immunology, Cytokines/immunology, Dendritic Cells/*immunology, Diphtheria Toxin/genetics/immunology, Eosinophils/immunology, Inflammation/chemically induced/genetics/immunology, Lung/cytology/*immunology, Macrophages, Alveolar/immunology, Mice, Mice, Inbred BALB C, Mice, Transgenic, Ovalbumin/administration & dosage, Research Support, Non-U.S. Gov't, Th2 Cells/*immunology/transplantation|
|The Journal of Experimental Medicine|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
van Rijt, L.S, Jung, S, Kleinjan, A, Vos, N, Willart, M, Duez, C, … Lambrecht, B.N.M. (2005). In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. The Journal of Experimental Medicine. Retrieved from http://hdl.handle.net/1765/8412