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Department of Pulmonary Medicine, Erasmus Medical Center, 3015 GE Rotterdam, Netherlands

Address correspondence to Bart N. Lambrecht, Department of Pulmonary Medicine, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands. Phone: 31-10-408-7703; Fax: 31-10-408-9453; email: b.lambrecht{at}erasmusmc.nl

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.

Key Words: asthma • plasmacytoid dendritic cells • tolerance • mucosal immunity • regulatory T cell

The online version of this article contains supplemental material.

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• Osterholzer, J. J., Ames, T., Polak, T., Sonstein, J., Moore, B. B., Chensue, S. W., Toews, G. B., Curtis, J. L. (2005). CCR2 and CCR6, but Not Endothelial Selectins, Mediate the Accumulation of Immature Dendritic Cells within the Lungs of Mice in Response to Particulate Antigen. J. Immunol. 175: 874-883 [Abstract] [Full Text]  
• Padilla, J., Daley, E., Chow, A., Robinson, K., Parthasarathi, K., McKenzie, A. N. J., Tschernig, T., Kurup, V. P., Donaldson, D. D., Grunig, G. (2005). IL-13 Regulates the Immune Response to Inhaled Antigens. J. Immunol. 174: 8097-8105 [Abstract] [Full Text]  
• Dalgaard, J., Beckstrom, K. J., Jahnsen, F. L., Brinchmann, J. E. (2005). Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets. J. Leukoc. Biol. 77: 689-698 [Abstract] [Full Text]  
• Samsom, J. N., van Berkel, L. A., van Helvoort, J. M. L. M., Unger, W. W. J., Jansen, W., Thepen, T., Mebius, R. E., Verbeek, S. S., Kraal, G. (2005). Fc{gamma}RIIB Regulates Nasal and Oral Tolerance: A Role for Dendritic Cells. J. Immunol. 174: 5279-5287 [Abstract] [Full Text]  
• Smith, D. W., Nagler-Anderson, C. (2005). Preventing Intolerance: The Induction of Nonresponsiveness to Dietary and Microbial Antigens in the Intestinal Mucosa. J. Immunol. 174: 3851-3857 [Abstract] [Full Text]  
• van Rijt, L. S., Jung, S., KleinJan, A., Vos, N., Willart, M., Duez, C., Hoogsteden, H. C., Lambrecht, B. N. (2005). In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. JEM 201: 981-991 [Abstract] [Full Text]  
• Demedts, I. K., Brusselle, G. G., Vermaelen, K. Y., Pauwels, R. A. (2005). Identification and Characterization of Human Pulmonary Dendritic Cells. Am. J. Respir. Cell Mol. Bio. 32: 177-184 [Abstract] [Full Text]  
• Lundy, S. K., Lira, S. A., Smit, J. J., Cook, D. N., Berlin, A. A., Lukacs, N. W. (2005). Attenuation of Allergen-Induced Responses in CCR6-/- Mice Is Dependent upon Altered Pulmonary T Lymphocyte Activation. J. Immunol. 174: 2054-2060 [Abstract] [Full Text]  

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