PGE 2, an endogenous lipid mediator released in inflammatory conditions, affects both dendritic cell (DC) differentiation and maturation. Whereas the effect of PGE 2 on fully differentiated DC was studied extensively, little is known about its effects on DC differentiation. In this study, we show that bone marrow-derived DC generated in the presence of PGE 2 (DCp) acquire a proinflammatory profile; produce higher levels of proinflammatory cytokines/chemokines; express higher levels of MHC class II, costimulatory molecules, and TLRs; and exhibit increased activation of the NF-κB-signaling pathway. In addition, DCp exhibit a different IL-12/IL-23 profile than DC generated in the absence of PGE 2. The low IL-12 and high IL-23 production in LPS-stimulated DCp is associated with the down-regulation of p35 and the up-regulation of p19 expression, respectively. In agreement with the DCp proinflammatory phenotype and especially with the altered IL-12/IL-23 balance which strongly favors IL-23, DCp also affect T cell differentiation. In contrast to DC which favor Th1 differentiation, DCp promote Th17 and inhibit Th1/Th2 differentiation, in vitro and in vivo. Previous in vivo studies indicated that PGE 2 had a proinflammatory effect, especially in models of autoimmune diseases. Our results suggest that the proinflammatory effects of PGE 2 could be mediated, at least partially, through effects on differentiating DC and subsequent alterations in CD4+ T cell differentiation, resulting in the preferential development of pathogenic autoimmune Th17 cells.