急性移植物抗宿主病（GVHD）死亡率高，治疗困难，目前常采取强烈的免疫抑制，严重影响移植物抗白血病（GVL）效应。前期研究发现IL-2联合组蛋白H3K4甲基转移酶MLL1抑制剂MM-102、SETD7抑制剂PFI-2可上调调节性T细胞（Tregs），下调Th1、Th17细胞，且发现合适剂量药物不影响淋巴细胞的肿瘤杀伤功能。拟进一步通过过表达MLL1和SETD7证明MM-102和PFI-2通过不同甲基化位点减低H3K4甲基化及下调JAK/STAT1/STAT4、JAK/STAT3通路，联合IL-2活化JAK/STAT5通路以调控静息（naïve） T细胞分化，而后证明联合用药可减轻小鼠急性GVHD，最后通过细胞分选、肿瘤细胞共培养及动物荷瘤模型证明联合用药不影响NK及T细胞的抗肿瘤活性从而可能保留GVL效应。此方案从疾病源头及表观遗传学水平出发，有望为急性GVHD治疗开辟安全、长效的新路径。

Now acute graft versus-host disease (GVHD) is the main obstacle of allogeneic hematopoietic stem cell transplantation because of high mortality and difficulty of treatment. Strong immune suppression was often adopted, which severely affected GVL effect. We found that interleukin-2 combined with histone H3K4 methyltransferase MLL1 inhibitors MM-102 and SETD7 inhibitors PFI-2 could upregulate regulatory T cells (Tregs) , downregulate Th1, Th17 cells and preserve anti-tumor fuction of lymphocyte. We would further overexpress MLL1 and SETD7 to clarify MM-102 and PFI-2 could reduce H3K4 methylation on different sites so as to inactivate JAK/STAT1/STAT4, JAK/STAT3 pathways, IL-2 activate JAK/STAT5 pathway so as to modulate naïve T cell differentiation. Combination medicine could alleviate mice acute GVHD and preserve graft versus leukemia effect without affecting anti-tumor function of NK cells and T cells. This method is expected to open safe and effective path for acute GVHD from the oringin of the disease and the epigenetic level of treatment .