免疫炎症反应是急性肾损伤（AKI）病理生理过程中的关键环节，浆细胞样树突状细胞(pDC)是一类在机体免疫炎症中起重要作用的树突状细胞亚群，但其在AKI中的作用尚不清楚。我们的前期研究发现，AKI时肾脏pDC浸润增加伴干扰素-α(IFN-α)表达上调，AKI前清除pDC可以缓解肾脏损伤，提示pDC在AKI的重要作用。目前未见关于AKI时pDC的作用及其机制的研究。据此我们提出假说：AKI时pDC浸润至肾脏局部并分泌IFN-α，促进肾脏炎症及肾小管上皮细胞损伤，加重AKI进程。本项目将结合pDC条件性敲除小鼠，从分子、细胞及动物水平多层次明确pDC是AKI时重要的致病免疫细胞，探讨肾脏招募pDC的机制，确定pDC通过分泌IFN-α促进AKI，揭示IFN-α促进肾脏炎症及肾小管上皮细胞结构及功能异常的机制。本项目将从致病性免疫细胞这个新视点探讨AKI的发生机制，为临床AKI的防治提供新思路。

The pathogenesis of acute kidney injury (AKI) involves intrarenal inflammation. Plasmacytoid dendritic cell (pDC) is a unique DC subset that orchestrates immune responses. However, its role in AKI remains unknow. In our pre-study, pDC infiltratration and increased IFN-α production in kidney was observed after AKI. Meanwhile, delepleting pDC before AKI was associated with reduced kidney injury, indicating a pathogenic role of pDC in the disease. However, to date the potential role of pDC in AKI and its underlying mechanism remains unknown. We hypothesize that pDC infiltrates into kidney and secretes IFN-α upon injury, promotes intrarenal inflammation and proximal tubular cells injury, thus exacerbating AKI. In this project, using pDC conditional knockout mice and experiments at the molecular, cellular and in vivo level, we will provide solid evidence that pDC activation leading to increased IFN-α production to be a major mechanism in the kidney inflammation and proximal tubular cells desfunction. This project will highlight the pivotal role of unique immune cell subset- pDC in the pathogenesis of AKI, which can represent a new therapeutic approach for AKI therapy in the future.