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

^a Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea;
^b Division of Transplantation/Immunotherapy, National Cancer Center Hospital, Tokyo, Japan;
^c Kirin Brewery Company, Tokyo, Japan;
^d Pharmacology Division, Research Institute, National Cancer Center, Tokyo, Japan;
^e Department of Pediatrics, Chonnam National University Medical School, Gwangju, Republic of Korea;
^f National Cancer Center Hospital, Tokyo, Japan

Key Words. Blood • Dendritic Cells • Th1/Th2 • Cell trafficking

Yoichi Takaue, M.D., Hematopoietic Stem Cell Transplant Unit, National Cancer Center Hospital, 1-1 Tsukiji 5-Chome, Chuo-ku, Tokyo 104-0045, Japan. Telephone: 81-3-3542-2511; Fax: 81-3-3542-3815; e-mail: ytakaue{at}ncc.go.jp

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-3ß 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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