Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen

Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present...

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Bibliographic Details
Published in:The Journal of experimental medicine 2004-07, Vol.200 (1), p.89-98
Main Authors: de Heer, Hendrik Jan, Hammad, Hamida, Soullié, Thomas, Hijdra, Daniëlle, Vos, Nanda, Willart, Monique A M, Hoogsteden, Henk C, Lambrecht, Bart N
Format: Article
Language:English
Subjects:
Administration, Inhalation
Animals
Antigens - administration & dosage
Antigens - immunology
Asthma - immunology
Asthma - pathology
Dendritic Cells - cytology
Dendritic Cells - immunology
Lung - cytology
Lung - metabolism
Mice
Mice, Inbred BALB C
Mice, Transgenic
Ovalbumin - immunology
Respiratory Hypersensitivity - immunology
T-Lymphocyte Subsets - immunology
T-Lymphocytes - immunology
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Summary:Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20040035