2005-03-21
In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma
Publication
Publication
The Journal of Experimental Medicine , Volume 201 - Issue 6 p. 981- 991
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.
Additional Metadata | |
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doi.org/10.1084/jem.20042311, hdl.handle.net/1765/54081 | |
The Journal of Experimental Medicine | |
Organisation | Department of Otorhinolaryngology |
van Rijt, L., Jung, S., Kleinjan, A., Vos, N., Willart, M., Duez, C., … Lambrecht, B. (2005). In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. The Journal of Experimental Medicine, 201(6), 981–991. doi:10.1084/jem.20042311 |