FTY720 alleviated the symptoms of acute GVHD by inhibiting the distribution of matured DCs

Abstract

Objective To investigate the role of FTY720, an agonist of the sphingosine 1-phos-phate （S1P） receptor, in acute graft-versus-host disease （aGVHD） caused by allogeneic hematopoietic stem cell transplantation and to further elucidate its possible mechanism .Methods BALB/c （ H2 d ） recipient mice were given whole body lethal irradiation （750 cGy） for 4 hours.A mouse model of aGVHD was estab-lished by intravenously injecting recipient mice with 1×10^7 C57BL/6 （H2b） mice derived bone marrow cells （BMCs） and 5×106 whole splenic cells.FTY720 （3 mg/kg） was intraperitoneally injected into recipient mice from the day before allogeneic bone marrow transplantation （ allo-BMT） to day 4 thereafter to monitor the survival rate .The mice in control group were perfused with equal volume of control reagent .Fluores-cence-activated cell sorting （ FACS） was used to analyze the phenotypes of immune cells in spleen , liver, lung as well as intestines of mice on the fourth day of allo-BMT with or without FTY720 treatment. Results FTY720 significantly prolonged overall survival in mice with allo-BMT induced aGVHD .FACS analysis showed that FTY720 significantly inhibited the distribution of matured dendritic cells （ DCs） in lung and small intestines .Conclusion FTY720 could significantly alleviate the symptom of aGVHD in mice received allogeneic hematopoietic stem cell transplantation .The possible mechanism might be associated with the inhibited distribution of matured DCs in lung and intestines . Key words: S1P; S1P receptor agonist; Endothelial cells; Chemokine; Graft-versus-host disease