| Successful human pregnancy requires the correct formation of the placenta. During placentation, extraembryonic cytotrophoblast stem cells differentiate along two distinct pathways to form an interface between fetal and maternal circulations. Mononuclear stem cells fuse to form syncytiotrophoblasts, whose primary function is to mediate nutrient, waste, and gas exchange for the developing fetus. Alternately, cytotrophoblasts differentiate to acquire an invasive phenotype, then migrate through the endometrium and disrupt maternal arteries. This process serves both to anchor the placenta to the uterine wall and to supply the fetus with nutrient-rich arterial blood. The consequence of cytotrophoblast differentiation is the mixing of genetically foreign fetal cells with large numbers of maternal cells, including leukocytes.; In light of this, the fact that the mother accepts the placenta as an allograft remains a great biological mystery. No single hypothesis appears to explain fetal evasion of the maternal immune system. Thus, it is likely that multiple protective mechanisms exist to ensure that viviparity succeeds. One of these is the localized secretion of factors that can modulate a potentially deletrious immune response. Various molecules produced by different placental cells have been shown to suppress immune function. Among them are cytokines, pleiotropic factors that play a role in the regulation of the growth and differentiation of a variety of cell types, including those of the immune system.; Our work has focused on the characterization of cytokine secretion by cytotrophoblast cells. Using an in vitro system that models uterine invasion by cytotrophbolasts, we found that these cells produce interleukin (IL)-10. We provide evidence that cytotrophoblast IL-10 has two important functions in vitro: (1) the paracrine suppression of allogeneic T lymphocyte reactions, and (2) the autocrine inhibition of cytotrophoblast invasion. Our results suggest that cytotrophoblast secretion of IL-10 at the maternal-fetal interface in vivo may dampen a maternal immune response and regulate placental attachment. |
