STAT5/STAT3转录因子活化与Treg/Th17细胞平衡在慢性移植物抗宿主病发病中的作用

Chronic graft versus host disease (cGvHD) are potentially lethal complications after stem cell transplantation (SCT).Because little was known about the cGvHD pathogenesis, the effective treatments of cGvHD were lacking.Our previous data showed that donor Th17 cells contributed to the pathogenesis of cGVHD.Meanwhile,there are controversial conclusions demonstrated by different units according to the correlationship between donor Treg cells and the occurrence of cGVHD.However, there was close relationship between the development of Th17 and Treg cells.It suggested that the ratio of Treg/Th17 cells might play more important roles in the pathogenesis of cGVHD. The relative basic study had showed that STAT5/STAT3 pathway were the key elements in regulating the balance of Treg/Th17 cells and low dose of IL2 could alter the Treg/Th17 balance through the STAT5/STAT3 pathway. Therefore, the aims of this study were to build the cGVHD mice model to investigate the roles of Treg/Th17 ratio on the deveolpment of cGVHD and to demonstrate that low dose of IL2 adminstration in the cGVHD mice model or in patients after transplantation could expand Treg cells and reduce the development of Th17 cells in vivo through influencing the STAT5/STAT3 pathway, therefore preventing the development of cGVHD. Furthermore, randomized and controlled study would be further collected to demonstrate that low dose of IL2 administrated early post-transplantation would reduce the probability of cGVHD occurrence, therefore increasing the efficiency of the transplantation.

移植后慢性移植物抗宿主病（cGVHD）发病率高，治疗效果差，严重影响患者生存质量，原因为目前cGVHD的发病机制不清，故缺乏有效治疗手段。我们前期工作显示Th17细胞与移植后cGVHD的发病呈正相关，而Treg细胞在cGVHD中的作用相关报道结论不一；相关基础研究显示Th17与Treg分化发育密切相关，提示Treg/Th17细胞平衡可能在cGVHD发病中起重要作用。而STAT5/STAT3转录因子是调节Treg/Th17细胞平衡的主要途径之一，且IL2可通过STAT5/STAT3影响Treg/Th17细胞平衡。本研究旨在通过建立cGVHD小鼠动物模型，证实Treg/Th17细胞平衡在cGVHD发病中的作用；并通过动物实验及临床研究证实，移植后早期体内应用小剂量IL2可通过影响STAT5/STAT3转录因子活化，调节Treg/Th17细胞平衡，降低cGVHD的发生率，改善患者移植预后。