异基因造血干细胞移植（Allo-HSCT）是血液恶性肿瘤有效乃至唯一的治疗手段，急性移植物抗宿主病（aGvHD）仍是移植后最常见和严重的并发症之一，如何防治aGvHD而不影响移植物抗白血病效应，即有效诱导免疫耐受是Allo-HSCT的关键科学问题。具有免疫抑制功能的新型髓系调节细胞：髓源性抑制细胞（MDSCs），对获得性免疫和天然免疫具有广泛调控功能，但人/鼠MDSCs表型迥异阻碍其在Allo-HSCT中的机制研究及临床转化。课题组前期发现移植物组分中人单核系MDSCs降低aGvHD风险，其功能分子2’3 IDO也与aGvHD存在相关性，推测单核系MDSCs可能通过2’3 IDO抑制aGvHD。本研究拟利用高度免疫缺陷的NPG小鼠制作人源化小鼠移植模型，通过免疫细胞输注及靶分子封闭/替代，旨在阐明体内单核系MDSCs在aGvHD发病中的作用及靶点，以期为新的aGvHD防控策略奠定基础。

Allogeneic Hematopoietic stem cell transplantation（Allo-HSCT）is the effective and sometimes the only curative treatment for the hematological malignancy, however, acute graft-versus-host disease(aGvHD) is still one of the most common and severe complication which decrease the therapeutic effect of Allo-HSCT. It’s a significant scientific question to prevent aGvHD without interference with graft-versus-leukemia effect (GVL), which means effective induction of immune tolerance. The new negative immune regulatory myeloid cells: myeloid-derived suppressor cells(MDSCs) have been found remarkable suppressive effects on both adaptive and innate immune responses. It was found in our previous work that monocytic subgroups of MDSCs（M-MDSCs）, expanded by G-CSF in allo-graft and secreting 2’3 IDO，were associated with lower risk of aGvHD post transplantation. Therefore, we predict M-MDSCs may play critical roles in immune tolerance induction. In this research we will investigate the underlying effects and mechanism of M-MDSCs on aGVHD in vivo with NPG humanized mice models. In sum, this investigation would contribute to the understanding of immune tolerance regulated by MDSCs in Allo-HSCT and prepare for the clinical applications.