Abstract
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. FTY720 treatment was performed using Foxp3(-) CD4(+) T cells purified from NOD mice. 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. 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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