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 a...

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Bibliographic Details
Published in:The Journal of experimental medicine 2005-03, Vol.201 (6), p.981-991
Main Authors: van Rijt, Leonie S, Jung, Steffen, Kleinjan, Alex, Vos, Nanda, Willart, Monique, Duez, Catherine, Hoogsteden, Henk C, Lambrecht, Bart N
Format: Article
Language:English
Subjects:
Adoptive Transfer
Aerosols - administration & dosage
Allergens - administration & dosage
Allergens - immunology
Animals
Asthma - chemically induced
Asthma - genetics
Asthma - immunology
CD11c Antigen - genetics
CD11c Antigen - immunology
Cytokines - immunology
Dendritic Cells - immunology
Diphtheria Toxin - genetics
Diphtheria Toxin - immunology
Eosinophils - immunology
Inflammation - chemically induced
Inflammation - genetics
Inflammation - immunology
Lung - cytology
Lung - immunology
Macrophages, Alveolar - immunology
Mice
Mice, Inbred BALB C
Mice, Transgenic
Ovalbumin - administration & dosage
Th2 Cells - immunology
Th2 Cells - transplantation
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20042311