HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal Niche - PubMed (original) (raw)

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

Silvia Gregori et al. Front Immunol. 2015.

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.

Keywords: HLA-G; IL-10; T regulatory cells; dendritic cells; trophoblasts; vascular remodeling.

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Figures

Figure 1

Figure 1

Proposed model for cross-talk among embryo trophoblasts, decidual leukocytes, and stromal cells at the maternal–fetal interface in human first trimester pregnancy. EVTs express and secrete HLA-G, and release IL-10 (and TSLP), which instruct dAPCs to become tolerogenic DC (i.e., dDC-10 or TSLP-modulated dDC) secreting IL-10 and promoting the induction of a variety of Tregs (i.e., Tr1 cells, CD4+CD25+FOXP3+ Tregs, and CD4+HLA-G+ Tregs). Induced Tregs inhibit effector T cells, and, via IL-10 secretion, promote HLA-G expression on EVTs. EVTs via HLA-G directly promote dNK cell activation and the release of angiogenic factors. dDC-10 is HLA-G+ and can interact with either dNKs or dMΦ via ILT2, and promote their activation and pro-angiogenic effects. dDC-10 themselves secrete also pro-angiogenic factors supporting neo-vascularization. HSPs secreted by the maternal cells and trophoblasts contribute to the regulation of HLA-G expression on dAPCs and EVTs. Finally, IL-10 modulates the UPR pathway and regulates vascular uterine remodeling by HLA-G+ EVTs.

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