Endoglin Regulates Intercellular Interactions between Trophoblast and Natural Killer Cells

The interaction of natural killer and trophoblast cells underliesmaternal-fetal immune tolerance. The data on the participation ofendoglin (ENG, CD105), or its soluble form, in the regulation ofthe communication of these cells are currently insufficient. Inthis study, we have investigated the role of endoglin in the intercellularinteractions between natural killer cells and trophoblasts. Here,we show that NK-92 cells and JEG-3 cells constitutively expressMICA/B, and CD105. In the presence of JEG-3 cells, the expressionof NKG2D, CD94, MICA/B, and CD105 by NK-92 cells was increased,and the number of NK-92 cells expressing NKG2A, CD94, and MICA wasreduced. Antibodies against ENG and recombinant endoglin (rENG),attenuated the trophoblasts’ influence and returned the phenotype ofthe NK-92 cells to that of cells found in monoculture conditions.The antibodies and rENG also increased the expression of pSMAD2/3by NK cells in both monoculture and co-culture conditions. The antibodiesincreased the trophoblasts’ sensitivity to the cytotoxic effectof NK cells. In general, our findings indicate a significant roleof endoglin in the intercellular communication between NK cellsand trophoblasts. We also speculate that endoglin forms a complexwith TGFβ, which aids in TGFβ trafficking between these cells.