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

Abstract

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, Clec4nmice had decreased Th2 immune response following HDM challenge, which may ascribe to dramatically reduced type 2 conventional dendritic cells (cDC2s) in lung of Clec4nmice, as cDC2s from lung of Clec4nmice 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.