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.
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.
Authors: Aina Teniente-Serra; José Vicente Hervás; Bibiana Quirant-Sánchez; María José Mansilla; Laia Grau-López; Cristina Ramo-Tello; Eva María Martínez-Cáceres Journal: CNS Neurosci Ther Date: 2016-04-15 Impact factor: 5.243
Authors: Mithun Khattar; Ronghai Deng; Barry D Kahan; Paul M Schroder; Tammy Phan; Lynne P Rutzky; Stanislaw M Stepkowski Journal: Transplantation Date: 2013-04-15 Impact factor: 4.939