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A more recent version of this article appeared on April 1, 2008

Published online before print January 8, 2008
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0307153

Received for publication March 12, 2007.
Revised October 11, 2007.
Accepted for publication December 1, 2007.

Article

Plasticity of dendritic cell function in response to prostaglandin E2 (PGE2) and interferon-{gamma} (IFN-{gamma})

Manfred Lehner , Andrea Stilper , Patrick Morhart , and Wolfgang Holter @

Laboratory of Cellular Therapy, Department of Hematology and Oncology, Children’s University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

@ To whom correspondence should be addressed. E-mail: wolfgang.holter{at}kinder.imed.uni-erlangen.de.


  Abstract

Current evidence suggests that maturing dendritic cells (DCs) acquire a migratory phenotype to induce T cell responses in lymph nodes or a proinflammatory phenotype to condition the microenvironment at peripheral sites. We show that the interplay of PGE2 and IFN-{gamma} generates a more complex pattern of mixed DC phenotypes in response to TLR stimulation. DCs activated by the TLR ligand R-848 in the presence of IFN-{gamma} and PGE2 produced high levels of IL-12p70 and IL-23, started migration toward CCL19 within only 10 h, and still continued to secrete IL-12p70 without further restimulation following the migration step. The accelerated onset of migration was a result of PGE2 and was associated with reduced plastic adherence and lower amounts of activated CD29. In contrast, IFN-{gamma} by itself enhanced cell adhesion and strongly hindered CCR7-mediated migration in the absence of PGE2. This suggests a new role for IFN-{gamma} in the direct regulation of DC migration through enhanced cell adhesion, perhaps to support the development of T cell effector functions at peripheral sites. Together, our data are relevant to the development of DC vaccines, as they demonstrate the existence of dual-functional DCs, which as a result of the simultaneous effects of PGE2 and IFN-{gamma}, can migrate rapidly toward lymph node chemokines and carry with them a wave of primary cytokines.

Key Words: R-848 • migration • CCR7






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