An adoptive cell therapy with TREM2‐overexpressing macrophages mitigates the transition from acute kidney injury to chronic kidney disease

作者：Yating Zhang, Jie Liu, Siweier Luo, Hanzhi Liang, Chipeng Guo, Yufei Du, Hongyu Li, Le Wang, Xiaohua Wang, Chun Tang, Yiming Zhou · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70252 · 被引用次数：11 · 研究领域：Inflammation biomarkers and pathways、Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer

BACKGROUND: Macrophages have been shown to contribute to renal injury and fibrosis as well as repair. Recently, Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)-positive macrophages have been shown to play important roles in regulating tissue inflammation and repair. However, it remains unclear whether they can mitigate the transition from acute kidney injury to chronic kidney disease (the AKI-CKD transition). METHODS: The AKI-CKD transition was generated by unilateral ischaemia-reperfusion injury (UIRI) in wild-type (WT) and Trem2 knockout mice. F4/80 magnetic beads were used to isolate renal macrophages. Flow cytometry was used to determine the levels of TREM2 and CD11b levels. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and histological staining were performed to determine the expression of cytokines and fibrotic markers. RNA-seq was used to investigate transcriptomic changes between WT and Trem2 knockout bone marrow-derived macrophages (BMDMs). TREM2-overexpressing macrophages were generated using lentivirus and transferred intravenously to UIRI mice. RESULTS: TREM2 macrophages exhibited a strong renal protective effect on the AKI-CKD transition. Genetic deletion of Trem2 resulted in increased renal inflammation and exacerbated renal injury and fibrosis in UIRI mice. Interestingly, we found that hypoxia could increase TREM2 expression in macrophages via HIF-1α. Upregulated TREM2 expression enhanced macrophage phagocytos...