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.