The sphingosine-1-phosphate receptor agonist FTY720 and its phosphorylated form affect the function of CD4+CD25+ T cells in vitro

  • Authors:
    • Yong Liu
    • Jingjing Jiang
    • He Xiao
    • Xiaokui Wang
    • Yan Li
    • Yubo Gong
    • Yifei Huang
  • View Affiliations

  • Published online on: April 20, 2012     https://doi.org/10.3892/ijmm.2012.973
  • Pages:211-219
0

Abstract

The sphingosine-1-phosphate receptor agonist FTY720 and FTY720-P have a wide variety of fundamental functions. Many studies have demonstrated that CD4+CD25+ regulatory T (Treg) cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Although FTY720 has also recently shown to possess an additional effect that increases the functional activity of Treg cells, the mechanism leading to the enhanced Treg activity after FTY720 treatment is still not clear. We isolated Treg cells, which were co-cultured with FTY720 or FTY720-P. The proliferation of co-cultured Treg cells was detected by the cell counting kit-8. The changes of the phenotype CD25+ and forkhead box P3 (Foxp3)+ of co-cultured Treg cells were measured by flow cytometry. The levels of IL-10 and TGF-β1 in the supernatants were detected by Elisa. Cytokine mRNA expressions in co-cultured Treg cells were analyzed by real-time quantitative PCR. Mixed lymphocyte reaction assay examined the suppressive function. We found that neither FTY720 nor FTY720-P affected the proliferation of co-cultured Treg cells. The percentages of CD25+ and Foxp3+ were enhanced in the high-dose FTY720-P group. The levels of TGF-β1 in the supernatants were enhanced in the high-dose FTY720 group. Medium and high-dose FTY720-P also enhanced the levels of TGF-β1. TGF-β1 and Foxp3 mRNA expression were upregulated in the high-dose FTY720-P group. The proliferation of effector T (Teff) cells was suppressed significantly in the medium and high-dose FTY720-P group at a Treg/Teff cell ratio of 1:1. At a ratio of 1:1, the proliferation of Teff cells was also suppressed in the high-dose FTY720 group. It can be concluded that high-dose FTY720-P can enhance the immune function of co-cultured Treg cells, and that medium-dose FTY720-P and high-dose FTY720 could partly enhance the function. The reason may be attributed to enhanced levels of TGF-β1 and Foxp3.

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July 2012
Volume 30 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Liu, Y., Jiang, J., Xiao, H., Wang, X., Li, Y., Gong, Y., & Huang, Y. (2012). The sphingosine-1-phosphate receptor agonist FTY720 and its phosphorylated form affect the function of CD4+CD25+ T cells in vitro. International Journal of Molecular Medicine, 30, 211-219. https://doi.org/10.3892/ijmm.2012.973
MLA
Liu, Y., Jiang, J., Xiao, H., Wang, X., Li, Y., Gong, Y., Huang, Y."The sphingosine-1-phosphate receptor agonist FTY720 and its phosphorylated form affect the function of CD4+CD25+ T cells in vitro". International Journal of Molecular Medicine 30.1 (2012): 211-219.
Chicago
Liu, Y., Jiang, J., Xiao, H., Wang, X., Li, Y., Gong, Y., Huang, Y."The sphingosine-1-phosphate receptor agonist FTY720 and its phosphorylated form affect the function of CD4+CD25+ T cells in vitro". International Journal of Molecular Medicine 30, no. 1 (2012): 211-219. https://doi.org/10.3892/ijmm.2012.973