Uterine natural killer (uNK) cells and their missions during pregnancy: a review

Natural killer (NK) cells are lymphocytes of the innate immune system. The aim of this review is to describe the properties and roles of NK cells in the human uterus during pregnancy. Uterine natural killer cells (uNK) constitute a major lymphocyte population during early gestation in the uterus. The uterine natural killer cells are recognized owing to their CD56(bright), CD16(-), CD3(-) phenotype. Their number increases in the first trimester with a subsequent decline as pregnancy progresses. They have been shown to be closely associated with cells of the extravillous trophoblast (EVT) and spiral arteries. They play important roles in remodeling of the spiral arteries, control of trophoblast invasion and in the development of the placenta. Some studies have shown the number and repertoire of receptors of uNK differ between women with healthy pregnancies and those with pathologic pregnancies, such as pre-eclampsia or intrauterine growth retardation. During pregnancy, the cytotoxic characteristics of the uterine killer cells are not directed towards the fetus, and scientists continue to question and explore this phenomenon with increasing evidence that these cells may perform differing beneficial roles during pregnancy. Contrary to their previously suspected "hostile" characteristics, the uterine killer cells are considered to be "friendly" and appear to be essential and very important regulators of successful implantation and pregnancy.