Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that can stimulate resting T cells in the primary immune response. During the maturation process, immature DCs lose their ability to internalize antigens and they acquire the capacity to present antigens to naive T cells. Many observations have suggested that distinct DC subsets might differentially regulate Th responses. However, recent reports suggest that specific subsets of either murine or human DCs cultured in vitro with different stimuli respond with great plasticity in terms of both gene expression and cytokine secretion. Thus, the microenvironment of DCs may determine the nature of mature DCs and the subsequent immune response. The mechanism by which the character of DCs is determined is unknown. The in vitro maturation process of human monocyte-derived DCs (MoDC) can be initiated by various stimuli. Many stimuli induce phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 MAPK in DCs during maturation. Such kinase-specific inhibitors help to reveal the functions of MAPKs in the maturation of human MoDCs. Recent studies suggest that three MAPK signaling pathways differentially regulate all aspects of phenotypic maturation, cytokine production, and functional maturation of MoDCs. Thus, distinct maturation of DCs may be induced by modulating the balance of phosphorylation of the three MAPKs. In this review, we summarize the role of MAPK signaling pathways in the maturation of human MoDCs.