Natural Killer cells: keepers of pregnancy in the turnstile of the environment

Abstract

During early pregnancy, an orchestrated endocrine-immunological scenario of maternal adaptation toward tolerance of the semiallogeneic fetus is required. Mechanisms preventing fetal loss by protecting the immune privilege of the gravid uterus, i.e. Galectin-1 or regulatory T cells, have recently been identified. Further, the presence of a unique population of Natural Killer (NK) cells, in humans identified by their CD56(+++)Galectin (Gal)-1(+)CD16(-) phenotype in the uterine lining (decidua), has been proposed to be a pivotal aspect of maternal adaptation to pregnancy. Decidual NK (dNK) cells comprise the largest population of immune cells during the first trimester in human decidua and control trophoblast invasion and vascular remodeling through their ability to secrete an array of angiogenesis-regulating molecules, chemokines and cytokines. A wealth of environmental factors, such as smoking, altered nutrition, pollution or stress has been proposed to peril not only pregnancy, but also fetal development. Further, published evidence supports that NK cells act as sentinel cells and environmental challenges can change their phenotype, e.g. via epigenetic pathways. We here review the effect of environmental factors, largely stress perception, on NK cells and its implication for pregnancy, fetal development and general health. As NK cells may not only be passive responders to the environment, but can also be 'educated and licensed', we propose novel strategies aiming to take advantage of the versatility of NK cells in maintaining immunosurveillance and tissue homeostasis.