title: FTY720-induced conversion of conventional Foxp3- CD4+ T cells to Foxp3+ regulatory T cells in NOD mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.forename: Jingfang
authors.initials: J
authors.lastname: Di
authors.forename: Linlin
authors.initials: L
authors.lastname: Chen
authors.forename: Lingling
authors.initials: L
authors.lastname: Ren
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000517:prevention & control; D005260:Female; D000068876:Fingolimod Hydrochloride; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011247:Pregnancy; D011409:Propylene Glycols / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000819:agonists; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine