Plasticity of dendritic cell function in response to prostaglandin E2 (PGE2) and interferon-gamma (IFN-gamma).
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 PGE(2) 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 PGE(2) 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 PGE(2) 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 PGE(2). 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 PGE(2) and IFN-gamma, can migrate rapidly toward lymph node chemokines and carry with them a wave of primary cytokines.
Lehner
Manfred
M
Laboratory of Cellular Therapy, Department of Hematology and Oncology, Children's University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Loschgestr. 15, D-91054, Erlangen, Germany.
Stilper
Andrea
A
Morhart
Patrick
P
Holter
Wolfgang
W
D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D004548:Elasticity; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D007093:Imidazoles; D005576:Colforsin; D007371:Interferon-gamma; D015232:Dinoprostone; C402365:resiquimod