急性肾损伤（AKI）发病率高，危害大，在肾移植中不可避免。AKI的核心是炎症，髓系来源的抑制性细胞（MDSC）是固有免疫中的重要免疫调节细胞。我们研究发现MDSC存在可塑性，其前体细胞e-MDSC在肾移植术后AKI患者外周血中显著降低，而单核系M-MDSC显著增高，且高于非移植术后AKI患者。我们进一步研究e-MDSC的代谢水平，发现移植AKI患者e-MDSC中线粒体自噬被显著抑制；通过鉴定相关脂质代谢谱后我们发现ACSF3酶可促进e-MDSC向M-MDSC分化。据此我们提出如下科学假说：AKI启动后的反馈保护机制促使e-MDSC向M-MDSC分化，其机制可能为ACSF3依赖的丙二酸代谢通路所抑制的线粒体自噬。本项目将聚焦“脂代谢依赖的线粒体自噬在MDSC可塑性中的机制”这一关键科学问题，通过临床样本及体内外实验模型，阐明其中的分子机理，并通过对关键靶点的干预，建立AKI治疗新策略。

Acute kidney injury (AKI) has a high incidence, which is inevitable in kidney transplantation and cause severe consequences. The main pathogenesis of AKI is inflammation. Myeloid-derived suppressor cells (MDSC) are important immunoregulatory cells in innate immunity. Our study found that MDSC has plasticity, and its precursor cell e-MDSC was significantly decreased in peripheral blood of AKI patients after renal transplantation, while mononuclear M-MDSC was significantly higher than that of non-transplant AKI patients. We further studied the metabolic levels of e-MDSC and found that mitochondrial autophagy was significantly inhibited in e-MDSC in kidney transplant recipients with AKI. By identifying the relevant lipid metabolism profiles, we found that ACSF3 enzymes can promote the differentiation of e-MDSC into M-MDSC. Based on these results, we propose the following scientific hypothesis: The feedback protection mechanism after AKI initiation promotes the differentiation of e-MDSC into M-MDSC, and its mechanism might be mitochondrial autophagy inhibited by ACSF3-dependent malonate metabolic pathway. Thus, our project will focus on the key scientific issue of "the mechanism of lipid metabolism-dependent mitochondrial autophagy in MDSC plasticity". The molecular mechanisms are elucidated through clinical samples and in vitro and in vivo experimental models, and established through intervention of key targets. This project will provide a new strategy of AKI treatment.