调节性T细胞在急性肾损伤发病机制中的作用。

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Xiaoyou Liu, Jianmin Hu, Guorong Liao, Ding Liu, Song Zhou, Jie Zhang, Jun Liao, Zefeng Guo, Yuzhu Li, Siqiang Yang, Shichao Li, Hua Chen, Ying Guo, Min Li, Lipei Fan, Liuyang Li, Ming Zhao, Yongguang Liu
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引用次数: 0

摘要

急性肾损伤(AKI)的发病率呈上升趋势,并与高死亡率有关;然而,目前很少有有效的治疗方法。此外,Tregs和免疫微环境(IME)的其他成分在AKI发病机制中的关系尚不清楚。我们从基因表达综合数据库(GEO)下载了四个可公开访问的AKI数据集,即GSE61739、GSE67401、GSE19130、GSE81741、GSE1 9288和GSE106993。此外,我们从南方医科大学珠江医院器官移植科收集了两份肾脏单细胞测序(scRNA-seq)样本,以研究慢性肾移植排斥反应(CKTR)。此外,我们还从GSE131685中采集了三份正常肾组织样本。通过分析AKI组和非AKI组之间免疫细胞的差异,我们发现非AKI的Treg数量明显多于AKI组。此外,信号通路的激活,如炎症分子分泌、免疫反应、糖酵解代谢、NOTCH、FGF、NF-κB和TLR4,在AKI组中显著高于非AKI组。此外,对单细胞测序数据的分析显示,慢性肾排斥反应患者和正常肾组织中的Tregs具有不同的生物学特性,包括免疫激活、细胞因子产生以及NOTCH和TLR4等信号通路的激活部分。在这项研究中,我们发现AKI和非AKI之间的IME存在显著差异,包括Tregs细胞和生物重要信号通路激活水平的差异。Tregs与炎症反应、炎症分子分泌、免疫激活、糖酵解等信号通路活性较低有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The role of regulatory T cells in the pathogenesis of acute kidney injury

The role of regulatory T cells in the pathogenesis of acute kidney injury

The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis.

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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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