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Plasticity of dendritic cell function in response to prostaglandin E 2 (PGE 2 ) and interferon‐γ (IFN‐γ)
Author(s) -
Lehner Manfred,
Stilper Andrea,
Morhart Patrick,
Holter Wolfgang
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0307153
Subject(s) - ccl19 , microbiology and biotechnology , biology , c c chemokine receptor type 7 , proinflammatory cytokine , dendritic cell , chemokine , immunology , cell migration , t cell , cell , inflammation , immune system , chemokine receptor , genetics
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‐γ 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‐γ 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‐γ by itself enhanced cell adhesion and strongly hindered CCR7‐mediated migration in the absence of PGE 2 . This suggests a new role for IFN‐γ 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‐γ, can migrate rapidly toward lymph node chemokines and carry with them a wave of primary cytokines.