异基因造血干细胞移植(HSCT)是造血系统恶性疾病以及遗传异常所致疾病的重要治疗手段。移植物中T细胞具有清除患者体内残留白血病/肿瘤细胞的移植物抗肿瘤（GVL）效应，也能导致移植物抗宿主病（GVHD）发生。因此，减轻GVHD并保留GVL是移植免疫近期研究重点。本课题组前期研究发现组蛋白去乙酰化酶抑制剂丙戊酸（VPA）能显著降低小鼠移植模型aGVHD严重程度，其机制可能与抑制T细胞组蛋白去乙酰化酶3（HDAC3），上调Akt蛋白乙酰化、降低磷酸化水平，并进一步抑制Th1和Th17T细胞有关。在此基础上，本课题组拟通过建立T细胞Hdac3条件性敲除小鼠模型，验证干预HDAC3-Akt调控轴对GVHD和GVL的免疫调控效应，证实调变Akt蛋白乙酰化和磷酸化对抑制GVHD和保留/促进GVL的调控作用。本研究为造血干细胞移植免疫调控和治疗提供新靶点，为HDAC3新型特异性抑制剂研发提供关键实验依据。

Allogeneic hematopoietic stem cell transplantation (HSCT) is an important treatment for hematopoietic malignancies and diseases caused by genetic abnormalities. T cells in the graft have the effect of graft-versus-leukemia (GVL) leading to eradicate residual leukemia / tumor cells, and can also provocate graft-versus-host disease (GVHD). Thus, the reduction of GVHD and retention of GVL is the focus of recent studies on transplant immunization. In this study, preliminary results found that histone deacetylase inhibitor valproic acid (VPA) significantly reduced the severity of aGVHD in mice transplant model, suggesting that the mechanism may be related to inhibition of histone deacetylase 3 (HDAC3), Akt acetylation and phosphorylation levels, inhibition of Th1/Th17 cells..In this study, we will investigate the effect of HDAC3-Akt on the regulation of GVHD and GVL by establishing a T-cell Hdac3 knockout mouse model, and confirm the regulation of Akt protein acetylation and phosphorylation on GVHD and GVL levels, Which provides a new target for the regulation and treatment of hematopoietic stem cell transplantation and provides a key basis for the subsequent development of new HDAC3 specific inhibitor.