National Taiwan University, Taiwan
Title: FcRI -chain negatively modulates Dectin-1 responses in dendritic cells Ching-Liang Chu
Biography: Ching-Liang Chu
The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FceRI g-chain (FcRg) has been found in many immune functions; however, the role of these adapters is not known in C-type lectin receptor (CLRs) response. In this report, we identified that FcRg, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRg or both DAP12 and FcRg enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes. In addition, increment of recall T-cell proliferation was observed in FcRg-deficient mice. Examining the Dectin-1 signaling, we revealed that the activations of several signaling molecules were augmented in FcRg-deficient DCs stimulated with Dectin-1 ligands. Furthermore, we demonstrated that the association of phosphatases SHP-1 and PTEN with FcRg may contribute to the negative regulation of FcRg in Dectin-1 activation in DCs. These results extend the inhibitory effect of ITAM-containing adapters to Dectin-1 response in immune functions, even though Dectin-1 contains an ITAM-like intracellular domain. According to the role of Dectin-1 in responding to microbes and tumor cells, our finding may have applications in the development of vaccine and cancer therapy.