Ai-Hua Liao

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

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.

What are the roles of macrophages and monocytes in human pregnancy

During pregnancy, the maternal immune system is challenged by the semi-allogeneic fetus, which leads to systemic and local immunity. Systemic immunity, including enhanced innate immunity with increased activation of monocytes, is induced by various placental factors. Maternal immune adaptations are most evident at the feto-maternal interface, where macrophages are enriched and communicate with various decidual leukocytes. These cells are not only contributing to the protection of the growing fetus from microorganisms, but also aiding placental development by promoting trophoblast invasion and spiral artery remodeling, and the parturition process. Thus, monocytes and macrophages concurrently play important roles throughout the trimesters. Dysregulation of these cells may thus lead to pregnancy complications, such as pre-eclampsia and preterm labor. In this review, monocytes and macrophage subsets and their roles in normal and pathological pregnancies are reviewed.

Recent Insight into the Role of the PD-1/PD-L1 Pathway in Feto-Maternal Tolerance and Pregnancy

Pregnancy presents a great challenge to the maternal immune system. Given that maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to serve a central function in altering the maternal immune responses. Regulatory T cells (Tregs) and the PD‐1/PD‐L1 pathway are both critical in controlling the immune responses. Recent studies have proved the critical function of the PD‐1/PD‐L1 pathway in regulating the T‐cell homeostasis and the peripheral tolerance through promoting the development and function of Tregs, and inhibiting the activation of effector T cells. The function of the PD‐1/PD‐L1 pathway in feto‐maternal interface and pregnancy has been investigated in human and animal models of pregnancy. In this review, we provide recent insight into the role of the PD‐1/PD‐L1 pathway in regulating T‐cell homeostasis, maternal tolerance, and pregnancy‐related complications as well as its possible applicability in clinical immunotherapy.

Treg Cells Are Negatively Correlated with Increased Memory B Cells in Pre‐eclampsia While Maintaining Suppressive Function on Autologous B‐Cell Proliferation

The objective of this study was to determine the simultaneous changes and the correlation between circulating regulatory T (Tregs) and B‐cell subsets in normal pregnancy (NP) and pre‐eclampsia (PE). Meanwhile, the regulatory function of Tregs on B‐cell proliferation was evaluated in vitro.

Quantitative reduction of peripheral CD4+ CD25+ FOXP3+ regulatory T cells in reproductive failure after artificial insemination by donor sperm.

The objective of this study was to determine whether peripheral Treg‐cell percentages were altered in women with reproductive failure after artificial insemination by donor sperm (AID) and which parameters can best discriminate women with AID failure and normal controls.

Morphological Changes and Expression of Cytokine After Local Endometrial Injury in a Mouse Model

Objective: To establish a mouse model for endometrial injury and determine the underlying mechanism regarding its favorable effect on embryo implantation. Study Design: Female Kunming mice were randomly allocated into 4 groups: group I, normal control; group II, injury procedure control; and group III and group IV, the mice being scratched with a blunt syringe on the right uterine horn or both, respectively. All the mice were mated with the males during the next estrus phase. The number of implanted embryos on each side of uterus was calculated on day 8 of pregnancy. The endometrial samples were taken on day 4 of pregnancy, and the local morphological changes and cytokine expressions were examined. Results: Compared to group II, our results showed that in group IV (1) there were significantly higher numbers of implanted embryos, (2) the endometrial glands and vasculatures in stroma were obviously increased and the pinopodes were abundant and well developed, and (3) the local levels of cytokines leukemia inhibitory factor (LIF) and oncostatin M (OSM) messenger RNA and protein expression were significantly increased. Conclusions: Local mechanical injury on mouse uteri enhanced endometrial receptivity and improved embryo implantation, which were correlated with the characteristic changes in endometrial morphology and the upregulation of LIF and OSM gene and protein expression.

CD14++CD16+HLA-DR+ Monocytes in Peripheral Blood are Quantitatively Correlated with the Severity of Pre-eclampsia

We aim to investigate the proportion and absolute counts of peripheral blood monocyte subsets in women with normal pregnancy (NP) and pre‐eclampsia (PE), and their correlation with the clinical manifestation and severity of PE.

ORIGINAL ARTICLE: Functional Changes of Human Peripheral B-Lymphocytes in Pre-Eclampsia

Problem  The aim of our study was to investigate the functional changes of human peripheral B‐lymphocytes in healthy and pre‐eclamptic pregnancies.

Functional changes of human peripheral B-lymphocytes in pre-eclampsia.

Problem  The aim of our study was to investigate the functional changes of human peripheral B‐lymphocytes in healthy and pre‐eclamptic pregnancies.

Immunological function of vitamin D during human pregnancy

The well‐established classic role of vitamin D is implicated in the regulation of the balance between calcium and phosphorus. Furthermore, vitamin D is also involved in many non‐classic physiological processes, mainly including the regulation of cell proliferation, differentiation, apoptosis and immune function, participation in the inflammatory response and maintenance of genome stability function. During pregnancy, vitamin D receptor and its metabolic enzymes are expressed at the placenta and decidua, indicating the potential role in the mechanism of immunomodulation at the maternal‐fetal interface. The insufficiency or deficiency of vitamin D may affect the mother directly and is related to specific pregnancy outcomes, such as preeclampsia, gestational diabetes, and recurrent miscarriage. This article reviews the effects of vitamin D on immune regulation during pregnancy.