Cutting edge: Alternative signaling of Th17 cell development by sphingosine 1-phosphate.
Sphingosine 1-phosphate (S1P) in blood and lymph controls T cell traffic and proliferation through type 1 S1P receptor (S1P(1)) signals, but suppression of IFN-gamma generation has been the only consistently observed effect on T cell cytokines. The fact that S1P enhances the development of Th17 cells from Ag-challenged transgenic S1P(1)-overexpressing CD4 T cells suggested that the S1P-S1P(1) axis may promote the expansion of Th17 cells in wild-type mice. In a model of Th17 cell development from CD4 T cells stimulated by anti-CD3 plus anti-CD28 Abs and a mixture of TGF-beta1, IL-1, and IL-6, S1P enhanced their number and IL-17-generating activity the same as IL-23. As for IL-23 enhancement of Th17 cell development, that by S1P was prevented by IL-4 plus IFN-gamma and by IL-27. The prevention of S1P augmentation of Th17 cell development by the S1P receptor agonist and down-regulator FTY720 implies that FTY720 immunosuppression is attributable partially to inhibition of Th17-mediated inflammation.
Liao
Jia-Jun
JJ
Department of Medicine and Department of Microbiology-Immunology, University of California, San Francisco, CA 94143, USA.
Huang
Mei-Chuan
MC
Goetzl
Edward J
EJ
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents; D053759:Interleukin-23 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
D015704:CD4 Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D053759:Interleukin-23; D008246:Lysophospholipids; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D019869:Phosphatidylinositol 3-Kinases; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine