The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats.
The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats.
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PD-1/PD-L1 抑制通路在先兆子痫中发生改变并调节先兆子痫大鼠中的 T 细胞反应
DOI：
10.1038/srep27683
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发表时间：
2016-06-09
影响因子：
4.6
通讯作者：
Liao A
中科院分区：
文献类型：
--
作者：
Tian M;Zhang Y;Liu Z;Sun G;Mor G;Liao A
程序性细胞死亡-1（PD-1）/PD-配体1（PD-L1）通路通过促进调节性T（Treg）发育和抑制效应T（如Th 17）细胞应答，对免疫稳态至关重要。然而，PD-1/PD-L1通路与Treg/Th 17失衡之间的关联尚未在先兆子痫（PE）中得到充分研究。在本研究中，我们观察到Treg和Th 17细胞的百分比之间呈负相关，并且与正常妊娠相比，PE中两个亚群上的PD-1和PD-L1的表达也发生了变化。我们通过L-NG-Nitroarginine Methyl Ester（L-NAME）诱导的大鼠PE样模型进一步探讨了它们之间的关系。PD-L1-Fc蛋白的给药通过抑制PI 3 K/AKT/m-TOR信号传导和增强PTEN表达逆转Treg/Th 17失衡，对先兆子痫模型提供了对母亲和胎儿的保护作用。此外，我们还观察到PD-L1-Fc通过逆转胎盘损伤对胎盘的保护作用。这些结果表明，PD-1/PD-L1通路的改变导致PE中Treg/Th 17失衡。PD-L1-Fc治疗对先兆子痫模型具有保护作用，表明PD-L1-Fc的使用可能是PE治疗的潜在治疗靶点。
The programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis by promoting regulatory T (Treg) development and inhibiting effector T (such as Th17) cell responses. However, the association between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance has not been fully investigated in pre-eclampsia (PE). In this study, we observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 on the two subsets also changed in PE compared with normal pregnancy. We further explored their relationshipin vivousing the L-NG-Nitroarginine Methyl Ester (L-NAME) induced PE-like rat models, also characterized by Treg/Th17 imbalance. Administration of PD-L1-Fc protein provides a protective effects on the pre-eclamptic models, both to the mother and the fetuses, by reversing Treg/Th17 imbalance through inhibiting PI3K/AKT/m-TOR signaling and enhancing PTEN expression. In addition, we also observed a protective effect of PD-L1-Fc on the placenta by reversing placental damages. These results suggested that altered PD-1/PD-L1 pathway contributed to Treg/Th17 imbalance in PE. Treatment with PD-L1-Fc posed protective effects on pre-eclamptic models, indicating that the use of PD-L1-Fc might be a potential therapeutic target in PE treatment.