Implication of the MAPK pathways in the maturation of human dendritic cells induced by nickel and TNF-alpha.

After application of haptens to the skin, immature dendritic cells (DC), also named Langerhans cells (LC), come into a maturation process, which include disappearance of specific molecules such as E-cadherin and Langerin and the expression of new molecules such as CD83, CD86 and CCR7. The involvement of p38 MAPK in DC maturation induced by haptens and TNF-alpha has already been shown, however, the role of the other MAPK, ERK and JNK, is less described. In this study, we demonstrated on human CD34(+)-derived DC that the three MAPK are participating to the expression of CD83, CD86 and CCR7 induced by nickel (NiSO(4)) but not to the down-regulation of E-cadherin and Langerin. In contrast, following TNF-alpha stimulation, only p38 MAPK is involved in CD83 and CCR7 expressions and ERK inhibits DC maturation while JNK inhibition had no effect. Our results also suggest that activation of p38 MAPK by TNF-alpha could partially suppress ERK activation and abrogates the inhibitory effect of ERK on DC maturation. In summary, the three MAPK pathways regulate DC maturation induced by haptens while only p38 MAPK seems to play a key role after TNF-alpha addition.