The Role of PGE₂in the Differentiation of Dendritic Cells: How Do Dendritic Cells Influence T‐Cell Polarization and Chemokine Receptor Expression?

Abstract

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.

Cigarette Smoke Extract Suppresses Human Dendritic Cell Function Leading to Preferential Induction of Th-2 Priming

“…cells into Th-1 cells (45), and contributes to the maturation of human DCs through the induction of IL-12 production (46). Although enhanced PGE 2 release by CSE-conditioned DCs may explain their preferential Th-2 priming, PGE 2 is unlikely to be accountable for the diminished T cell priming capacity or CCR7 up-regulation observed in CSE-conditioned DCs.…”

E-Prostanoid (EP)2/EP4 Receptor-Dependent Maturation of Human Monocyte-Derived Dendritic Cells and Induction of Helper T2 Polarization

“…In accordance with a previous report (Brossart et al, 1998), the population of the adherent cells was composed of Ͼ90% CD14 ϩ cells. The remaining adherent cells were cultured in RPMI 1640 medium, including GM-CSF (50 ng/ml) and IL-4 (50 ng/ml) for 6 days and generated into immature MoDCs as described previously (Lee et al, 2002). In other cases, monocytes were isolated from PBMCs by counterflow centrifugation using the elutriator system (JE-6B-elutriator system; Beckman Coulter Inc., Fullerton, CA).…”

KIR2DS1-dependent acquisition of CCR7 and migratory properties by human NK cells interacting with allogeneic HLA-C2+ DCs or T-cell blasts

“…Values are given as the chemotactic index compared with the migration of unstimulated NK cells. 10,21 As further confirmation, migrated cells were counted also by flow cytometry (absolute count) (BD Flow Sensor option, FACSVerse) (not shown).…”