In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma

LS Van Rijt, S Jung, A KleinJan, N Vos… - The Journal of …, 2005 - rupress.org
LS Van Rijt, S Jung, A KleinJan, N Vos, M Willart, C Duez, HC Hoogsteden, BN Lambrecht
The Journal of experimental medicine, 2005rupress.org
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 …
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.
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