IL-25 Receptor Expression on Airway Dendritic Cells after Allergen Challenge in Subjects with Asthma

RATIONALE: IL-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and that has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs may play a protective role in asthma and are key players in the innate immune response through recognition of microbial products via Toll-like receptors (TLRs). The effects of inhaled allergens on the expression of IL-17RB by mDCs and pDCs, and the effects of IL-25 on pDCs, are unknown. OBJECTIVES: To evaluate allergen-induced changes in IL-17RB expression by mDCs and pDCs and to investigate the effects of IL-25 on pDCs. METHODS: Patients with mild atopic asthma (n = 13) were challenged with inhaled allergen. Blood and sputum DCs were enumerated and IL-17RB expression was determined by flow cytometry before and 7 and 24 hours after allergen challenge. The effects of IL-25 on pDCs in vitro were also assessed. MEASUREMENTS AND MAIN RESULTS: Inhaled allergen significantly increased mDC and pDC numbers in sputum but not in blood. The percentage of IL-17RB(+) mDCs and pDCs was significantly increased in blood and sputum 24 hours after challenge. IL-25 up-regulated TLR9 expression by pDCs and orchestrated the responses to TLR9 ligation. CONCLUSIONS: IL-17RB is up-regulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.