消退素D1通过ALX/FPR2途径增加调节性T细胞百分比，从而预防缺血/再灌注诱导的急性肾损伤。
Resolvin D1 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Increasing Treg Percentages via the ALX/FPR2 Pathway.
作者信息
Luan Hong, Wang Chuanxiao, Sun Jianping, Zhao Long, Li Lin, Zhou Bin, Shao Shihong, Shen Xuefei, Xu Yan
机构信息
Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Thoracic Surgery, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
出版信息
Front Physiol. 2020 Apr 3;11:285. doi: 10.3389/fphys.2020.00285. eCollection 2020.
AIMS
To evaluate whether Resolvin D1 attenuates ischemia/reperfusion-induced (IRI) acute kidney injury (AKI) via affecting Tregs.
MATERIALS AND METHODS
The IRI-AKI mouse model was established, and RvD1 was injected into the mouse tail vein. Further, the renal function, histological changes, injury markers and serum cytokines were detected at 24 and 72 h after IRI. Flow cytometry was used to categorize regulatory T cells (Tregs) in the spleen and kidney. Treg cells were stripped with the anti-CD25 antibody blocker PC61 to assess its role in the protective effect of RvD1 on IRI mice. CD4 T cells were obtained from spleen monocytes by magnetic bead sorting and differentiated into induced Treg (iTreg) cells. The effect of RvD1 on iTreg cell differentiation was observed . In addition, neutralizing antibodies against the orphan receptor G-protein-coupled receptor 32 (anti-GPR32) and LXA4 receptor (anti-ALX/FPR2), both RvD1 receptor blockers, were used to evaluate the effect of RvD1 on iTreg cell differentiation. Boc-1, an ALX/FPR2 receptor inhibitor, was administered via the tail vein to observe its effects on the ameliorative efficacy of RvD1 in IRI-AKI mice .
RESULTS
, RvD1 increased Treg percentages, alleviated renal tubular injury and reduced the serum levels of IFN-γ, TNF-α and IL-6 in IRI-AKI mice, while PC61 depleted the number of Tregs and reversed the protective effects of RvD1. , RvD1 induced the generation of iTregs. Importantly, preincubation with anti-ALX/FPR2 neutralizing antibodies but not with anti-GPR32 neutralizing antibodies, abrogated the enhancement activity of RvD1 on iTregs. In addition, blockade of the receptor ALX/FPR2 by Boc-1 reversed the beneficial effects of RvD1 on the splenic and kidney Treg percentages, renal tubular injury and serum IFN-γ, TNF-α, and IL-6 levels.
CONCLUSION
Our study demonstrates that RvD1 protects against IRI-AKI by increasing the percentages of Tregs via the ALX/FPR2 pathway.
目的
评估还原型维甲酸D1（Resolvin D1）是否通过影响调节性T细胞（Tregs）减轻缺血/再灌注诱导的（IRI）急性肾损伤（AKI）。
材料与方法
建立IRI-AKI小鼠模型，并将RvD1注入小鼠尾静脉。此外，在IRI后24小时和72小时检测肾功能、组织学变化、损伤标志物和血清细胞因子。采用流式细胞术对脾脏和肾脏中的调节性T细胞（Tregs）进行分类。用抗CD25抗体阻断剂PC61去除Treg细胞，以评估其在RvD1对IRI小鼠保护作用中的作用。通过磁珠分选从脾脏单核细胞中获得CD4 T细胞，并将其分化为诱导性Treg（iTreg）细胞。观察RvD1对iTreg细胞分化的影响。此外，使用针对孤儿受体G蛋白偶联受体32（抗GPR32）和LXA4受体（抗ALX/FPR2）的中和抗体，这两种都是RvD1受体阻断剂，来评估RvD1对iTreg细胞分化的影响。通过尾静脉给予ALX/FPR2受体抑制剂Boc-1，观察其对RvD1改善IRI-AKI小鼠疗效的影响。
结果
RvD1增加了IRI-AKI小鼠中Treg的百分比，减轻了肾小管损伤，并降低了血清中IFN-γ、TNF-α和IL-6的水平，而PC61减少了Tregs的数量并逆转了RvD1的保护作用。RvD1诱导了iTregs的产生。重要的是，预先用抗ALX/FPR2中和抗体而非抗GPR32中和抗体孵育，消除了RvD1对iTregs的增强活性。此外，Boc-1对受体ALX/FPR2的阻断逆转了RvD1对脾脏和肾脏Treg百分比、肾小管损伤以及血清IFN-γ、TNF-α和IL-6水平的有益影响。
结论
我们的研究表明，RvD1通过ALX/FPR2途径增加Tregs的百分比来保护免受IRI-AKI的影响。
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