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 1×107 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 re-ceived allogeneic hematopoietic stem cell transplantation .The possible mechanism might be associated with the inhibited distribution of matured DCs in lung and intestines .

Objective To analyze the predictive value of serum interleukin-27 (IL-27) for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated donors. Methods Serum samples were collected from 72 patients after receiving allo-HSCT from unrelated donors during January to December 2012. Serum samples collected from 70 patients received allo-HSCT in 2013 were used for confirmation. All patients received myeloablative conditioning regimen prior to allo-HSCT. Cyclosporin A (CsA)+mycophenolate mofetil (MMF)+short-term methotrexate (MTX) were used for GVHD prophylaxis. Serum IL-27 levels in patients with aGVHD were measured by ELISA. The pre-dictive value of IL-27 index,defined as the ratio of serum IL-27 level at neutrophil engraftment to that before pre-conditioning regimen, for allogeneic HSCT was retrospectively analyzed. Results Serum IL-27 index was significantly decreased in patients with gradeⅡ-ⅣaGVHD(grade 0-Ⅰ : 1.89±0.68 vs gradeⅡ-Ⅳ :1.26±0.49;P<0.000 1). IL-27 index had good value for grade Ⅱ-Ⅳ aGVHD (AUC=0.782,95% CI:0.675-0.889,P<0.001). Patients with a lower serum IL-27 index (<1.33) were more likely to have a higher cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with a higher serum IL-27 index (P<0.001). Multivariate analysis confirmed that low IL-27 index was the most significant risk factor for gradeⅡ-Ⅳ aGVHD (HR=4.50,95% CI:2.1-9.8,P<0.01). These findings were consistent with the results found in the serum samples collected in 2013. Conclusion Low IL-27 index could be used to predict the incidence of grade Ⅱ-Ⅳ acute GVHD after allo-HSCT from unrelated donors.