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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-11-0017.
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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1354-1361
IMMUNOBIOLOGY
Prostaglandin E2 is a key factor for CCR7 surface expression
and migration of monocyte-derived dendritic cells
Elke Scandella,
Ying Men,
Silke Gillessen,
Reinhold Förster, and
Marcus Groettrup
From the Research Department and the Oncology
Department, Cantonal Hospital St Gallen, Switzerland, and the
Experimental Surgery and Immunology Section, University
Erlangen-Nürnberg, Erlangen, Germany.
Dendritic cells (DCs) are potent antigen-presenting cells
that are able to initiate and modulate immune responses and are hence
exploited as cellular vaccines for immunotherapy. Their capacity to
migrate from peripheral tissues to the T-cell areas of draining lymph
nodes is crucial for the priming of T lymphocytes. In this study, we
investigated how the maturation of human monocyte-derived DCs (MoDCs)
by several different stimuli under serum-free conditions affected their
T-cell stimulatory function, cytokine secretion, and migratory
behavior. Surprisingly, we found that for all maturation stimuli
tested, the addition of prostaglandin E2 (PGE2) was required for
effective migration of MoDCs toward the lymph node-derived chemokines
CCL19 (EBI1 ligand chemokine/macrophage inflammatory protein--3 ) and CCL21 (secondary lymphoid tissue chemokine
[SLC]/6Ckine). Costimulation with PGE2 enhanced the
expression of the CCL19/CCL21 receptor CCR7 on the cell surface of
MoDCs when they were matured with soluble CD40 ligand or
proinflammatory cytokines, but did not affect CCR7 expression of
polyI:C-stimulated MoDCs. The effects of PGE2 on MoDCs were mediated
through increased cyclic adenosine monophosphate by 2 of the known PGE2
receptors, EP2 and EP4, which are expressed and down-regulated after
PGE2 binding in these cells. In conclusion, our results suggest that
signals provided by the proinflammatory mediator PGE2 are crucial for
MoDCs to acquire potent T-helper cell stimulatory capacity and
substantial chemotactic responsiveness to lymph node-derived
chemokines. This is a new and important parameter for the preparation
of MoDCs as cellular vaccines in tumor immunotherapy.

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