Dectin-1 Plays an Important Role in House Dust Mite-Induced Allergic Airway Inflammation through the Activation of CD11b+ Dendritic Cells

It is well known that sensitization against fungi is closely associated with severity of asthma. Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component beta-glucan, as well as some component(s) in house dust mite (HDM) extract. However, the roles of Dectin-1 in HDM-induced allergic airway inflammation remain unclear. In this study, we used Dectin-1-deficient (Clec7a(-/-)) mice to examine whether Dectin-1 is involved in HDM-induced allergic airway inflammation. We found that HDM-induced eosinophil and neutrophil recruitment into the airways was significantly attenuated in Clec7a(-/-) mice compared with that in wild-type mice. In addition, HDM-induced IL-5, IL-13, and IL-17 production from mediastinum lymph node cells was reduced in HDM-sensitized Clec7a(-/-) mice. Dectin-1 was expressed on CD11b(+) dendritic cells (DCs), an essential DC subset for the development of allergic inflammation, but not on CD103(+) DCs, plasmacytoid DCs, or lung epithelial cells. Transcriptome analysis revealed that the expression of chemokine/chemokine receptors, including CCR7, which is indispensable for DC migration to draining lymph nodes, was decreased in Clec7a(-/-) DCs. In accordance with these results, the number of HDM-labeled CD11b(+) DCs in mediastinum lymph nodes was significantly reduced in Clec7a(-/-) mice compared with wild-type mice. Taken together, these results suggest that Dectin-1 expressed on CD11b(+) DCs senses some molecule(s) in HDM extract and plays a critical role in the induction of HDM-induced allergic airway inflammation by inducing the expression of chemokine/chemokine receptors in DCs.