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 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.
de Heer
Hendrik Jan
HJ
Department of Pulmonary Medicine, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands.
Hammad
Hamida
H
Soullié
Thomas
T
Hijdra
Daniëlle
D
Vos
Nanda
N
Willart
Monique A M
MA
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D010047:Ovalbumin