Mechanisms of CpG-induced CD40 expression on murine bone marrow-derived dendritic cells.

Aberrant CD40 expression by dendritic cells (DCs), induced by microbial stimuli, such as CpG, contributes to the pathogenesis of many human/murine diseases, particularly autoimmune and inflammatory diseases. Given the importance of CD40 in these diseases, and the contribution of DCs to the diseases process, it is very important to investigate the mechanisms of CD40 expression induced by CpG on DCs. In this study, we made the observation that CpG-B is a potent inducer on CD40 expression on murine bone marrow-derived DCs. Based on this finding, we undertook an analysis of the molecular basis of CpG-induced CD40 expression on DCs. By using selective inhibitors, it was demonstrated that MAPKs (JNK and p38 MAPK but not ERK) and NF-κB were involved in CpG-induced CD40 expression on DCs. In addition, RNA interference analysis revealed that IRF8 was a key transcription factor in the basal expression of CD40 upon CpG stimulation. Moreover, up-regulating miRNA-146a in DCs effectively decreased CD40 expression by targeting TRAF6 and IRAK1. Thus, our results have elucidated the molecular mechanisms underlying CpG-induced CD40 expression and DC maturation.