急性肾损伤（简称AKI）是临床常见的危重症，易于进展至慢性肾脏病（简称CKD），造成重大社会医疗负担。申请人既往研究证实：Foxp3+调节型T细胞（简称Tregs）功能紊乱是导致肾脏持续炎症损伤及AKI转归不良的关键致病因素。目前对于AKI中影响Tregs免疫表型的机制不清楚。最新研究提示Tet蛋白影响Tregs关键基因Foxp3的转录过程。我们的预实验结果证实：Tet激动剂能够显著提高AKI-CKD小鼠Tregs的免疫活性，减轻肾脏慢性炎症损伤及纤维化程度。我们推测：Tet介导的Tregs免疫活性是决定AKI转归的关键因素。为此，本课题将通过基因干预细胞实验、Tet基因敲除小鼠模型、Tregs移植实验及AKI临床研究，首次探讨Tet调控Tregs免疫表型在AKI转归的作用机制。本研究旨在阐明调控AKI炎症反应及其转归的新机制，为临床早期干预治疗开拓新思路，具有深远的科学意义和临床价值。

Acute kidney injury (AKI) is a critical disease that might progress to chronic kidney disease (CKD), resulting in significant social burden. Previous studies confirmed that dysfunction of Foxp3+ regulatory T cells (Tregs) is a causative factor that causes persistent renal inflammation and poor AKI outcomes. However, the mechanisms regulating Tregs immunity in AKI remain unclear. The latest studies suggested that Tet mediates the transcription process of Foxp3, which is a key regulator of Tregs immunity. Our preliminary data show that: Tet agonists significantly improve the immunosuppression activity of mouse Tregs, leading to reduced kidney inflammatory injury and fibrosis. We thus suggest that Tet dysfunction in AKI might result in Tregs abnormality, leading to ongoing kidney inflammation and chronic fibrosis. In this study, we will investigate the mechanisms of Tet-mediated Tregs immunity in AKI-CKD by cell culture experiments, Tet knockout mouse models, Tregs adoptive transfer, and clinical study of AKI. Our study aims to reveal the mechanism of Tregs immunity that involves in kidney inflammation and fibrosis after AKI. Our findings may open a new way to the understanding of Tregs immunity in acute and chronic kidney disorders.