移植物抗宿主病（GVHD）是异基因造血干细胞移植（HSCT）后的主要并发症和死亡原因。髓系来源的抑制性细胞（MDSC）是一群异质性的不成熟髓系细胞，发挥免疫负向调控功能。MDSC在aGVHD中的防治作用已明确，进一步探寻安全有效的体内/外扩增及增强其免疫抑制功能的方法已成为其走向临床应用的关键。我们前期研究发现，mTOR抑制剂雷帕霉素（RAPA）可显著提高MDSC抑制T细胞增殖的能力，而自噬抑制剂羟氯喹（HCQ）则可减弱MDSC的免疫抑制功能并可逆转由RAPA引起的免疫抑制功能的上调。本项目拟通过体内外研究探讨自噬对MDSC免疫抑制功能的调节作用及其机制，明确mTOR抑制剂通过mTOC1-ULKl途径调控MDSC的自噬水平来增强其免疫抑制功能的分子机制，并探讨其在aGVHD预防及治疗中的作用。本项目对于揭示MDSC免疫功能调控新机制，寻找aGVHD的有效防治新策略具有重大的理论和实际意义。

Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation（HSCT）. Myeloid-derived suppressor cells(MDSC) represent a heterogenic population of immature myeloid cells and are characterized by a strong ability to suppress various T cell functions. MDSC have a definite function in the prevention and treatment of aGVHD. To explore a safe and effective method of in vivo/vitro amplification and enhancing its immunosuppressive function has become the key point for its clinical application. In our previous study we have found that mTOR inhibitor rapamycin(RAPA) can remarkably improve the function of inhibiting T cell proliferation, while the autophagy inhibitor hydroxychloroquine(HCQ) can reduce the immunosuppressive function of MDSC and can reverse the up-regulation of immunosuppressive function cause by RAPA. Using mouse model and in vitro cell research, our current study will first clarify the roles and mechanisms of autophagy in enhancing the immunosuppressive function of MDSC, validate the hypothesis that mTOR inhibitors enhance the immunosuppression function of MDSC by regulating its autophagy level through the mTOC1 - ULK1 pathway.The research can reveal novel mechanisms of function regulation of MDSC and provide novel clues for aGVHD prevention and treatment.