Myeloid and plasmacytoid dendritic cells in induced sputum after allergen inhalation in subjects with asthma

Abstract

Dendritic cells are professional antigen presenting cells that mediate the response to inhaled allergens. In animal models, the induction and maintenance of allergic airway inflammation is primarily a function of myeloid dendritic cells, whereas the tolerization to inhaled allergens is likely a function of plasmacytoid dendritic cells. To investigate changes in sputum myeloid and plasmacytoid dendritic cells after allergen inhalation in subjects with asthma. Also, the number of myeloid and plasmacytoid dendritic cells expressing both CCR6 and 7 and their chemokine ligands macrophage inflammatory protein (MIP)-3alpha and 3beta were measured in sputum supernatants. Sputum was induced from 12 dual-responder subjects with allergic asthma before and 7 hours, 24 hours, and 72 hours after inhalation of diluent and allergen. Dendritic cells were enumerated via flow cytometry and the chemokines by using ELISAs. The number of sputum myeloid dendritic cells was significantly higher 24 hours after allergen challenge compared with diluent. Similarly, sputum plasmacytoid dendritic cells increased significantly at 24 hours after allergen challenge. Also, a significant increase in CCR6(+) myeloid dendritic cells numbers occurred 72 hours after allergen challenge. In contrast, CCR7(+) myeloid dendritic cells, as well as the number of CCR6(+) and CCR7(+) plasmacytoid dendritic cells, were not different between challenges. Finally, allergen challenge increased sputum levels of MIP-3alpha, but not MIP-3beta, compared with baseline. Both myeloid and plasmacytoid dendritic cells increase in the sputum of subjects with asthma after allergen challenge, suggesting that both subsets are involved in the pathogenesis of allergen responses in asthma.