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

• DOI: 10.1084/jem.20042311
• Publication Date: 2005-03-21T19:32:53Z
• Authors: Leonie S. van Rijt; Steffen Jung; Alex KleinJan; Nanda Vos; Monique Willart; Catherine Duez; Henk C. Hoogsteden; Bart N. Lambrecht
• Keywords: Aerosols; Inflammation; 0301 basic medicine; Mice, Inbred BALB C; Ovalbumin; Mice, Transgenic; Dendritic Cells; Allergens; EMC MM-04-42-02; Adoptive Transfer; Article; Asthma; CD11c Antigen; Eosinophils; Mice; 03 medical and health sciences; Th2 Cells; Macrophages, Alveolar; Animals; Cytokines; Diphtheria Toxin; Lung

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.