Interactions between canonical Wnt signaling pathway and MAPK pathway regulate differentiation, maturation and function of dendritic cells

Antigen-presenting dendritic cells interpret environmental signals to orchestrate local and systemic immune responses. In this study, the roles of Wnt proteins and their signaling pathway members in the maturation and function of monocyte-derived DCs were investigated. The present study showed higher expression of beta-catenin, as well as pGSK-3 beta in DCs than those in monocytes. Wnt3a, Wnt5a and inhibition of GSK-3 beta promoted differentiation of DCs, but inhibited maturation of DCs. GSK-3 beta induced DCs maturation with unconventional phenotypes. Together with beta-catenin silence, these treatment lead to reduced secretion of cytokines and chemokines except for IL-10 in comparison with LPS treatment, and significantly promoted proliferation of T cells. Wnt3a and inhibition of GSK-3 beta increased expression of MAPK signalings (p-ERK, p-p38, p-JNK). However, inhibition of MAPK signalings in turn differently regulated Wnt signaling proteins expression. These data suggest that Wnt pathway regulates DCs differentiation, maturation and function with interaction of MAPK signaling pathways. (C) 2016 Elsevier Inc. All rights reserved.