Published online before print January 8, 2008

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(Journal of Leukocyte Biology. 2008;83:883-893.)
© 2008 by Society for Leukocyte Biology

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

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

¹ Correspondence: Children’s University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Loschgestr. 15, D-91054, Erlangen, Germany. E-mail: wolfgang.holter{at}uk-erlangen.de

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- 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- 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- by itself enhanced cell adhesion and strongly hindered CCR7-mediated migration in the absence of PGE₂. This suggests a new role for IFN- 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-, 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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