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Sphingosine 1‐phosphate induces Chemotaxis of immature dendritic cells and modulates cytokine‐release in mature human dendritic cells for emergence of Th2 immune responses
Author(s) -
Idzko Marco,
Panther Elisabeth,
Corinti Silvia,
Morelli Anna,
Ferrari Davide,
Herouy Yared,
Dichmann Stefan,
Mockenhaupt Maja,
Gebicke-Haerter Peter,
Di Virgilio Francesco,
Girolomoni Giampiero,
Norgauer Johannes
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0625fje
Subject(s) - microbiology and biotechnology , biology , sphingosine 1 phosphate , immune system , sphingosine , dendritic cell , cytokine , chemotaxis , immunology , receptor , biochemistry
Sphingosine 1‐phosphate (S1P) is a potent extracellular lysolipid phosphoric acid mediator that is released after IgE‐stimulation of mast cells. Here we investigated the biological activity and intracellular signaling of S1P on human dendritic cells (DC), which are specialized antigen presenting cells with the ability to migrate into peripheral tissues and lymph nodes, as well as control the activation of naive T cells. We show that immature and mature DC express the mRNA for different S1P receptors, such as endothelial differentiation gene (EDG)‐1, EDG‐3, EDG‐5, and EDG‐6. In immature DC, S1P stimulated pertussis toxin‐sensitive Ca 2+ increase actin‐polymerization and chemotaxis. These responses were lost by DC matured with lipopolysaccharide. In maturing DC, however, S1P inhibited the secretion of tumor necrosis factor α and interleukin (IL)‐12, whereas it enhanced secretion of IL‐10. As a consequence, mature DC exposed to S1P showed a reduced and increased capacity to generate allogeneic Th1 and Th2 responses, respectively. In summary, our study implicates that S1P might regulate the trafficking of DC and ultimately favor Th2 lymphocyte‐dominated immunity.