Cutting edge: Alternative signaling of Th17 cell development by sphingosine 1-phosphate

J Immunol. 2007 May 1;178(9):5425-8. doi: 10.4049/jimmunol.178.9.5425.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4 Antigens / analysis
  • Cells, Cultured
  • Cytokines / pharmacology
  • Fingolimod Hydrochloride
  • Immunosuppressive Agents
  • Interleukin-23 / pharmacology
  • Lymphocyte Activation* / drug effects
  • Lysophospholipids / metabolism*
  • Lysophospholipids / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / metabolism
  • Propylene Glycols / pharmacology
  • Receptors, Lysosphingolipid / agonists
  • Receptors, Lysosphingolipid / antagonists & inhibitors
  • Receptors, Lysosphingolipid / metabolism*
  • Signal Transduction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Sphingosine / pharmacology
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • CD4 Antigens
  • Cytokines
  • Immunosuppressive Agents
  • Interleukin-23
  • Lysophospholipids
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • sphingosine 1-phosphate
  • Phosphatidylinositol 3-Kinases
  • Fingolimod Hydrochloride
  • Sphingosine