FTY720-Induced Conversion of Conventional Foxp3−CD4+ T Cells to Foxp3+ Regulatory T Cells in NOD Mice

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 Foxp3−CD4+ 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 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.