HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print January 8, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0307153v1 83/4/883    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lehner, M. Articles by Holter, W. PubMed PubMed Citation Articles by Lehner, M. Articles by Holter, W.

(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