Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses.
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 Ca2+ 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 alpha 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.
Idzko
Marco
M
Department of Experimental Dermatology of Freiburg, D-79104 Freiburg, Germany.
Panther
Elisabeth
E
Corinti
Silvia
S
Morelli
Anna
A
Ferrari
Davide
D
Herouy
Yared
Y
Dichmann
Stefan
S
Mockenhaupt
Maja
M
Gebicke-Haerter
Peter
P
Di Virgilio
Francesco
F
Girolomoni
Giampiero
G
Norgauer
Johannes
J
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002633:Chemotaxis; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008246:Lysophospholipids; D018448:Models, Immunological; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000199:Actins; D016207:Cytokines; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C060506:sphingosine 1-phosphate; D013110:Sphingosine; D002118:Calcium