The Role of PGE 2 in the Differentiation of Dendritic Cells: How Do Dendritic Cells Influence T‐Cell Polarization and Chemokine Receptor Expression?

The role of prostaglandin E 2 (PGE 2 ) in the function of dendritic cells (DCs), T‐cell polarization, and expression of chemokine receptors was evaluated in human cells. Immature DCs were generated from peripheral blood CD14 + cells using a combination of GM‐CSF and interleukin‐4 (IL‐4) with or without PGE 2 . On day 6, maturation of DCs was induced by the addition of tumor necrosis factor alpha with or without PGE 2 . DCs harvested on day 6 (immature DCs) or day 9 (mature DCs) were examined using functional assays. In the presence of PGE 2 , immature and mature DCs showed, phenotypically, a lower expression of CD1a and, functionally, a higher allostimulatory capacity at a high DC/T‐cell ratio than control cells cultured in the absence of PGE 2 . DCs cultured in the presence of PGE 2 induced the differentiation of naïve T cells toward a helper T‐cell type 1 (Th1) response, which was independent of IL‐12 secretion in the basal state despite a slightly lower interferon gamma secretion compared with control cells. However, the function of cytotoxicity‐stimulating autologous T cells was not augmented by the addition of PGE 2 . Immature DCs expressed the inflammatory chemokine receptors, CCR1 and CXCR4, but not CCR6, regardless of the presence or absence of PGE 2 . Mature DCs expressed CCR7 equally, measured using a migration test and the measurement of calcium flux with macrophage inflammatory protein‐3β and reverse transcription‐polymerase chain reaction assay in all of the groups. All of these findings suggest that PGE 2 affects the DC‐promoted differentiation of naïve T cells to a Th1 response in the basal state, without affecting chemokine receptor expression on DCs.