Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s

The role of Dectin-2 (gene symbol, Clec4n) in house dust mite (HDM) induced Th2 immune response and the exact mechanism remains controversial. In this study, we illustrated that, Clec4n^-/- mice had decreased Th2 immune response following HDM challenge, which may ascribe to dramatically reduced type 2 conventional dendritic cells (cDC2s) in lung of Clec4n^-/- mice, as cDC2s from lung of Clec4n^-/- mice after challenging had less ability to induce Th2 response with decreased production of IL-4/IL-13. Further in vitro experiments showed the activation of Clec4n^-/--BMDCs significantly decreased after HDM stimulation accompanied with decreased activation of Syk-NF-κB and Syk-JNK signal pathway. Importantly, Dectin-2 expression in PBMCs from asthmatic patients was significantly higher than that in healthy controls. Taken together, these results demonstrated that Dectin-2 could promote cDC2s activation in lung, which polarizes Th2 immune response outlining a novel mechanism of asthma development.