Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets. Blood 100:1362–1372

dritic cells (DCs) from sites of infection into draining lymphoid tissues is funda-mental to the priming of T-cell immune responses. We evaluated monocyte-de-rived DCs (MoDCs) and peripheral blood DCs (PBDCs) to respond to proinflamma-tory mediators, CD40L, and intact bacteria. All classes of stimuli induced DC pheno-typic maturation. However, for MoDCs, only prostaglandin E2 (PGE2)–containing stimuli induced migratory-type DCs. Thus, imma-ture MoDCs that encountered proinflamma-tory cytokines or CD40L or intact bacteria in the presence of PGE2 acquired migratory capacity but secreted low levels of cyto-kines. Conversely, MoDCs that encountered pathogens or CD40L alone become nonmi-gratory cytokine-secreting cells (proinflam-matory type). Interestingly, both migratory-and proinflammatory-type DCs expressed equivalent levels of chemokine receptors, suggesting that the role of PGE2 was to switch on migratory function. We demon-strate that PGE2 induces migration via the E-prostanoid 2/E-prostanoid 4 (EP2/EP4) re-ceptors and the cAMP pathway. Finally, mi-gratory-type MoDCs stimulated T-cell prolif-eration and predominantly IL-2 secretion, whereas proinflammatory-type MoDCs in-duced IFN- production. In contrast, CD1b/c PBDC rapidly acquired migratory capacity irrespective of the class of stimu-lus encountered and secreted low levels of cytokines. This suggests that not all mature stages of DCs are destined to migrate to lymphoid organs and that the sequence in which stimuli are encountered significantly affects which functions are expressed. Thus, certain immature DC subsets recruited from the resting precursor pool may have mul-tiple functional fates that play distinct roles during the induction and effector phases of the immune response. These findings have important implications for the clinical utility of DCs in immunotherapy. (Blood. 2002;100