髓系抑制性细胞（MDSCs）在移植免疫中发挥重要作用，既抑制适应免疫，也抑制天然免疫；不仅抑制效应T细胞，且诱导调节性T细胞，具有良好临床应用前景。MDSCs分化的调控机制研究将为MDSCs的应用提供必要理论基础。在前期工作基础上，我们将在本课题中主要集中于单核样MDSCs（M-MDSCs），进行：1）筛选和优化多种细胞因子配伍的诱导M-MDSCs的体系，建立能够大量产生抑制功能强大的M-MDSCs诱导体系，解析其发生的重要分子机制。2）确定目前临床常用免疫抑制剂等对M-MDSCs诱导和功能的影响特点，分析其主要分子路线。3）建立以M-MDSCs、免疫抑制剂及骨髓移植联合应用的移植免疫耐受诱导方案，明确该过程的重要细胞分子事件。我们相信通过该系列研究将加深我们对M-MDSCs发生机制的理解，为M-MDSCs的临床应用提供必要理论基础与技术，促进M-MDSCs在移植免疫耐受诱导的转化应用。

Myeloid-derived suppressor cells（MDSCs），mainly including monocytic MDSCs and granulocytic MDSCs participate in many physiological and pathological processes and caused significant attention. It has been confirmed that MDSCs played an important role in transplantation immune tolerance. MDSCs can inhibit both adaptive and innate immunity. MDSCs inhibit effector T cells but induce immunosuppressive Treg cells. All these made MDSCs become potential clinical therapy target cells during transplantation tolerance induction. The studies on the mechanisms of MDSC differentiation may provide the essential foundation and make sense for the clinical applications. On the basis of our recent related work, we will focus on the following issues: 1) We will establish the optimal M-MDSC induction system in vitro, and pursue the molecular mechanisms. 2) We will determine the effects of clinical immunosuppressive drugs on MDSC induction and function. And 3) we will establish the transplantation tolerance inducing regimen with the combination of M-MDSCs, immunosuppressive drugs and bone marrow transplantation. We believe that the proposed studies may enhance our understanding about the MDSCs generation and development mechanisms, offering the theoretical basis and techniques for the clinical application of MDSCs, and promoting the application of M-MDSCs in transplantation tolerance induction.