HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal Niche.

Silvia Gregori,Federica Quattrone,Paola Panina-Bordignon,Giada Amodio

doi:10.3389/fimmu.2015.00128

Abstract

Extravillous trophoblasts (EVTs) play a central role in educating maternal leukocytes, endometrial stromal and endothelial cells to generate a receptive decidual microenvironment tailored to accept the semi-allogeneic fetus. HLA-G, a non-classical HLA class I molecule endowed with immune-regulatory functions, is primarily expressed on EVTs lining the placenta and on the naturally occurring tolerogenic dendritic cells, named DC-10, which are enriched in the human first trimester decidua. Decidual DC-10 are involved in HLA-G-mediated tolerance at the maternal–fetal interface. EVTs not only establish a tolerogenic microenvironment through the interaction with maternal innate and adaptive cells but also orchestrate placenta vascular and tissue remodeling, leading to a successful pregnancy. Here, we discuss the potential implications of the HLA-G-mediated cross-talk among the cells present at the maternal–fetal interface, and its role in maintaining a positive relationship between the mother and the fetus.

Highlights

The maternal–fetal interface is composed of fetal trophoblasts intermingled with maternal leukocytes, stromal, and endothelial cells that comprise the decidua
The evidence that, after embryo implantation, defective development and function of extravillous trophoblasts (EVTs) can lead to fetal loss and pregnancyassociated pathological conditions, including pre-eclampsia and intrauterine growth restriction [2,3,4], sustains the important role of EVTs in orchestrating the decidual modification for successful pregnancy
The expression of HLA-G, a non-classical HLA class I molecule, on EVTs contributes to trophoblast invasiveness, decidual cell differentiation, vascular remodeling, and maintenance of a local immunosuppressive state

Summary

INTRODUCTION

The maternal–fetal interface is composed of fetal trophoblasts intermingled with maternal leukocytes, stromal, and endothelial cells that comprise the decidua. Trophoblasts, derived from the trophoectoderm surrounding the blastocyst, differentiate into the syncytiotrophoblasts that infiltrates the endometrium, and the cytotrophoblasts at the embryo side. The layer of syncytiotrophoblasts in contact with the decidua represents the extravillous trophoblasts (EVTs) (Figure 1). The evidence that, after embryo implantation, defective development and function of EVTs can lead to fetal loss and pregnancyassociated pathological conditions, including pre-eclampsia and intrauterine growth restriction [2,3,4], sustains the important role of EVTs in orchestrating the decidual modification for successful pregnancy. The expression of HLA-G, a non-classical HLA class I molecule, on EVTs contributes to trophoblast invasiveness, decidual cell differentiation, vascular remodeling, and maintenance of a local immunosuppressive state. A proper understanding of regulatory mechanisms that control EVTs interaction with the maternal niche is a critical issue in reproduction

STATE OF THE ART

Vascular remodeling Angiogenesis

Maternal endothelium Fetal vessels

Findings

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