• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Cellular and Molecular Immunology >The altered PD-1/PD-L1 pathway delivers the ‘one-two punch’ effects to promote the Treg/Th17 imbalance in pre-eclampsia
【2h】

The altered PD-1/PD-L1 pathway delivers the ‘one-two punch’ effects to promote the Treg/Th17 imbalance in pre-eclampsia

机译：改变后的PD-1 / PD-L1途径产生一两次冲动效应以促进先兆子痫中Treg / Th17失衡

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical for normal pregnancy by promoting regulatory T (Treg) cell development and inhibiting the Th17 response. However, the relationship between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance in pre-eclampsia (PE) is an enigma. In this study, decreased PD-1 and PD-L1 expression and a Treg/Th17 imbalance were observed at the maternal-fetal interface in PE. The regulatory effects of the PD-1/PD-L1 pathway on the Treg and Th17 cell quantities were determined in vitro by targeting T-cell proliferation, differentiation and transdifferentiation. First, decreased PD-1 expression might contribute to a higher Th17 cell frequency by promoting proliferation in PE. Second, the percentages of Treg but not Th17 cells differentiated from peripheral naive CD4+ T cells were increased by PD-L1 Fc administration. This effect was accompanied by decreased PI3K/AKT/m-TOR and increased PTEN mRNA expression and was completely reversed by PD-1 blockade. Finally, the percentage of IL-17-producing Treg cells increased and was positively associated with the Th17 cell frequency in PE. Increased RORγt and IL-17 but not Foxp3 and IL-10 mRNA expression by Treg cells was observed with PD-1 blockade. Similar findings occurred when Treg cells were exposed to IL-6/IL-23/IL-1β and were reversed by PD-L1 Fc. Taken together, our findings indicate that the PD-1/PD-L1 pathway contributes to the Treg/Th17 imbalance via ‘one-two punch’ approaches: (i) promoting Th17 cell proliferation, (ii) inhibiting Treg cell differentiation and (iii) enhancing Treg cell plasticity into Th17 cells in PE. The therapeutic value of PD-L1 Fc for PE treatment will be explored in the future.
机译：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）细胞发育并抑制Th17反应，对于正常妊娠至关重要。然而，先兆子痫（PE）中PD-1 / PD-L1途径与Treg / Th17不平衡之间的关系是一个谜。在这项研究中，在PE的母胎界面中观察到PD-1和PD-L1表达降低以及Treg / Th17不平衡。通过靶向T细胞增殖，分化和转分化，体外确定PD-1 / PD-L1途径对Treg和Th17细胞数量的调节作用。首先，降低的PD-1表达可能会通过促进PE的增殖而导致更高的Th17细胞频率。其次，通过施用PD-L1 Fc增加了从外周幼稚CD4 + T细胞分化而来的Treg而不是Th17细胞的百分比。该作用伴随着PI3K / AKT / m-TOR的降低和PTEN mRNA表达的提高，并被PD-1阻断完全逆转。最后，产生IL-17的Treg细胞的百分比增加，并且与PE中的Th17细胞频率呈正相关。用PD-1阻断剂观察到Treg细胞的RORγt和IL-17升高，但Foxp3和IL-10 mRNA表达没有升高。当Treg细胞暴露于IL-6 / IL-23 /IL-1β并被PD-L1 Fc逆转时，也会发生类似的发现。综上所述，我们的发现表明，PD-1 / PD-L1途径通过“一两拳”方法促进了Treg / Th17失衡：（i）促进Th17细胞增殖，（ii）抑制Treg细胞分化和（iii ）增强Treg细胞对PE中Th17细胞的可塑性。将来将探讨PD-L1 Fc在PE治疗中的治疗价值。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号