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Sci Rep. 2016 Jun 9;6:27683. doi: 10.1038/srep27683.

The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats.

Author information

1
Family Planning Research Institute, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
2
Department of Obstetrics and Gynecology, Maternal and Child Health Hospital of Hubei province, Wuhan, P.R. China.
3
Department of Obstetrics, Gynecology &Reproductive Sciences, Division of Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

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 relationship in vivo using 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.

PMID:
27277012
PMCID:
PMC4899740
DOI:
10.1038/srep27683
[Indexed for MEDLINE]
Free PMC Article

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