The Role of PGE2 in the Differentiation of Dendritic Cells: How Do Dendritic Cells Influence T-Cell Polarization and Chemokine Receptor Expression?

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Abstract

The role of prostaglandin E2 (PGE2) 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 PGE2. On day 6, maturation of DCs was induced by the addition of tumor necrosis factor alpha with or without PGE2. DCs harvested on day 6 (immature DCs) or day 9 (mature DCs) were examined using functional assays. In the presence of PGE2, 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 PGE2. DCs cultured in the presence of PGE2 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 PGE2. Immature DCs expressed the inflammatory chemokine receptors, CCR1 and CXCR4, but not CCR6, regardless of the presence or absence of PGE2. 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 PGE2 affects the DC-promoted differentiation of naïve T cells to a Th1 response in the basal state, without affecting chemokine receptor expression on DCs.

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