Regulatory T Cells as a Novel Candidate for Cell-Based Therapy in Kidney Disease
Regulatory T Cells as a Novel Candidate for Cell-Based Therapy in Kidney Disease
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调节性 T 细胞作为肾脏疾病细胞疗法的新候选者
DOI：
10.3389/fphys.2020.00621
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发表时间：
2020-06-09
影响因子：
4
通讯作者：
Liao, Pinhu
中科院分区：
文献类型：
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作者：
Lu, Junyu;Zhang, Jianfeng;Liao, Pinhu
肾脏疾病是世界范围内一个重要的健康问题。无效的治疗可能导致灾难性的后果，如器官衰竭和死亡。研究已经转向基于细胞的疗法，但尚未产生有效和可靠的治疗肾脏疾病的方法。为了解决这个问题，我们检查了人类、小鼠和大鼠患病和健康肾脏组织的四个基因表达谱数据集。筛选差异表达基因（DEGs）并进行富集分析。病变肾组织中上调基因在与调节性T细胞（Tregs）相关的通路中显著富集。用xCell工具分析显示，所有物种的病变肾脏组织中Tregs普遍升高。为了在体内验证这些结果，从阿霉素引起的肾病小鼠中取出肾脏，组织学证实Tregs增加。此外，将健康小鼠的Tregs过继转移到肾损伤小鼠体内，使受损肾脏的结构恢复正常。与M2c巨噬细胞共培养的Treg细胞显示趋化因子受体CCR2、CCR5、CCR7、CD62L和CX3CR1上调。这可能是M2c细胞促进Tregs向炎症部位迁移的机制。我们认为Tregs可能是临床前肾损伤模型中基于细胞治疗的一种有效的新候选药物。
Kidney disease is a significant health concern worldwide. Ineffective treatment can lead to disastrous consequences, such as organ failure and death. Research has turned to cell-based therapy, but has yet to produce an effective and reliable treatment for kidney disease. To address this problem, we examined four datasets of gene expression profiles from diseased and healthy kidney tissue in humans, mice, and rats. Differentially expressed genes (DEGs) were screened and subjected to enrichment analyses. Up-regulated genes in diseased kidney tissue were significantly enriched in pathways associated with regulatory T cells (Tregs). Analysis with the xCell tool showed that Tregs were generally increased in diseased kidney tissue in all species. To validate these results in vivo, kidneys were removed from mice with Adriamycin-induced nephropathy, and histology confirmed increase of Tregs. Furthermore, Tregs were adoptively transferred from healthy mice into mice with kidney injury, restoring normal structure to the damaged kidneys. Treg cells that were co-cultured with M2c macrophages exhibited up-regulation of chemokine receptors CCR2, CCR5, CCR7, CD62L, and CX3CR1. This may be the mechanism by which M2c cells enhance the migration of Tregs to the site of inflammation. We propose that Tregs may be an effective, novel candidate for cell-based therapy in pre-clinical kidney injury models.