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Updated: Jun 1, 2026
In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
FTY720-induced conversion of conventional Foxp3- CD4+ T cells to Foxp3+ regulatory T cells in NOD mice
Yun Sun1, Wenjing Wang, Bin Shan
1Department of Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
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 Foxp3(-) CD4(+) T cells to Foxp3(+) regulatory T cells in non-obese diabetic (NOD) mice.
Method Of Study:
FTY720 treatment was performed using Foxp3(-) CD4(+) 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 Foxp3(-) CD4(+) 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.
Insights
FTY720 treatment effectively converts conventional CD4(+) T cells into regulatory T cells (Tregs) in non-obese diabetic mice. This finding suggests FTY720 may be a therapeutic strategy for autoimmune and infectious diseases.
Area of Science:
- Immunology
- Endocrinology
Background:
- FTY720 (fingolimod) is a sphingosine-1-phosphate (S1P) receptor agonist.
- The capacity of FTY720 to induce regulatory T cell (Treg) conversion from conventional T cells in non-obese diabetic (NOD) mice remains largely unexplored.
Purpose of the Study:
- To investigate whether FTY720 can induce the conversion of Foxp3(-) CD4(+) T cells into Foxp3(+) Tregs in NOD mice.
- To assess the therapeutic potential of FTY720 in modulating T cell populations relevant to autoimmune diseases.
Main Methods:
- Purified Foxp3(-) CD4(+) T cells from NOD mice were treated with FTY720 in vitro and in vivo.
- The effects of FTY720 on Foxp3 expression and Treg cell populations were analyzed.
- The role of TGF-β and IL-6 in FTY720-induced Treg conversion was examined.
- T-cell-mediated embryo rejection was assessed in FTY720-treated NOD mice.
Main Results:
- FTY720 treatment significantly increased Foxp3(+) Treg cells in lymphoid organs of NOD mice.
- FTY720 effectively induced Foxp3 expression in Foxp3(-) CD4(+) T cells both in vitro and in vivo.
- This induction was partially inhibited by a TGF-β-neutralizing antibody and IL-6.
- FTY720 treatment prevented T-cell-mediated embryo rejection in NOD mice.
Conclusions:
- FTY720 promotes the conversion of conventional CD4(+) T cells into Foxp3(+) Tregs in NOD mice.
- Combining FTY720 with antigen administration may offer a therapeutic approach for expanding antigen-specific Tregs.
- This strategy holds promise for intervening in autoimmune and infectious diseases.
