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FTY720-Induced Conversion of Conventional Foxp3CD4+ T Cells to Foxp3+ Regulatory T Cells in NOD Mice

Authors

  • Yun Sun,

    1. Department of Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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    • These authors contributed equally.

  • Wenjing Wang,

    1. Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
    2. Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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    • These authors contributed equally.

  • Bin Shan,

    1. Department of Medicine, Tulane University Healthy Sciences Center, New Orleans, LA, USA
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    • These authors contributed equally.

  • Jingfang Di,

    1. Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou, China
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  • Linlin Chen,

    1. Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou, China
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  • Lingling Ren,

    1. Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou, China
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  • Weiping Li,

    1. Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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  • Da-Jin Li,

    1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
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  • Yi Lin

    1. Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
    2. Shanghai Key Laboratory of Gynecologic Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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Yi Lin, Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China. E-mail: yilinonline@gmail.com; or
Da-Jin Li, Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China. E-mail: djli@shmu.edu.cn

Abstract

Citation Sun Y, Wang W, Shan B, Di J, Chen L, Ren L, Li W, Li D-J, Lin Y. FTY720-induced conversion of conventional Foxp3CD4+ T cells to Foxp3+ regulatory T cells in NOD mice. Am J Reprod Immunol 2011; 66: 349–362

Problem  FTY720 is known as an agonist of sphingosine-1-phosphate (S1P) receptor, but little is known about the possibility that FTY720 induces the conversion of conventional Foxp3CD4+ T cells to Foxp3+ regulatory T cells in non-obese diabetic (NOD) mice.

Method of study  FTY720 treatment was performed using Foxp3CD4+ T cells purified from NOD mice.

Results  FTY720 caused an increase in Foxp3+ Treg cells in lymphoid organs in NOD mice. FTY720 effectively induced Foxp3 expression in Foxp3CD4+ T cells both in vitro and in vivo, an effect that was inhibited by a TGF-β-neutralizing antibody or the proinflammatory cytokine IL-6. T-cell-mediated embryo rejection in NOD mice was prevented upon FTY720 treatment.

Conclusions  The use of FTY720 along with Ag administration may represent a useful therapeutic strategy to selectively expand Ag-specific Foxp3+ Tregs to intervene autoimmune and infectious diseases.

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