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.
van Rijt
Leonie S
LS
Department of Pulmonary Medicine, Erasmus MC, 3015 GE Rotterdam, Netherlands.
Jung
Steffen
S
Kleinjan
Alex
A
Vos
Nanda
N
Willart
Monique
M
Duez
Catherine
C
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
D019264:Adoptive Transfer; D000336:Aerosols / Q000008:administration & dosage; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004167:Diphtheria Toxin / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation
D000336:Aerosols; D000485:Allergens; D039521:CD11c Antigen; D016207:Cytokines; D004167:Diphtheria Toxin; D010047:Ovalbumin