Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions.
Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions.
复制标题
间充质干细胞通过脾细胞相互作用诱导调节性 T 细胞减轻缺血性急性肾损伤
DOI：
10.1038/ki.2013.114
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发表时间：
2013-09
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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作者：
间充质干细胞治疗急性肾损伤的机制尚不清楚。先前的研究表明，间充质干细胞可以通过诱导调节性T细胞来减轻炎症相关的器官损伤。调节性T细胞诱导是否是缺血性急性肾损伤间充质干细胞治疗的潜在机制，以及这些诱导的调节性T细胞如何协调局部炎症尚不清楚。本研究发现，间充质干细胞可降低缺血肾的血清肌酐和尿素氮水平，改善肾小管损伤，并下调T细胞IFN-γ的产生。除肺外，间充质干细胞主要存在于脾脏。间充质干细胞增加了脾脏和缺血肾中调节性T细胞的百分比。调节性T细胞的抗体依赖性耗损削弱了间充质干细胞的治疗效果，而脾细胞与间充质干细胞共培养导致调节性T细胞百分比的增加。脾切除术消除了缺血损伤的衰减，下调了IFN-γ的产生和间充质干细胞对调节性T细胞的诱导。因此，间充质干细胞通过与脾细胞相互作用诱导调节性T细胞改善缺血性急性肾损伤。缺血肾中积累的调节性T细胞可能参与下调IFN-γ的产生。
The mechanism of mesenchymal stem cell therapy in acute kidney injury remains uncertain. Previous studies indicated that mesenchymal stem cells could attenuate inflammation-related organ injury by induction of regulatory T cells. Whether regulatory T-cell induction is a potential mechanism of mesenchymal stem cell therapy in ischemic acute kidney injury and how these induced regulatory T cells orchestrate local inflammation are unknown. Here we found that mesenchymal stem cells decrease serum creatinine and urea nitrogen levels, improve tubular injury, and downregulate IFN-γ production of T cells in the ischemic kidney. In addition to the lung, mesenchymal stem cells persisted mostly in the spleen. Mesenchymal stem cells increased the percentage of regulatory T cells in the spleen and the ischemic kidney. Antibody-dependent depletion of regulatory T cells blunted the therapeutic effect of mesenchymal stem cells, while coculture of splenocytes with mesenchymal stem cells caused an increase in the percentage of regulatory T cells. Splenectomy abrogated attenuation of ischemic injury, and downregulated IFN-γ production and the induction of regulatory T cells by mesenchymal stem cells. Thus, mesenchymal stem cells ameliorate ischemic acute kidney injury by inducing regulatory T cells through interactions with splenocytes. Accumulated regulatory T cells in ischemic kidney might be involved in the downregulation of IFN-γ production.