Part F: Functional Duality of Mouse Uterine Natural Killer Cell in Pregnancy

Uterine-natural killer (uNK) cells are a transient and dominant leukocyte in the uterine mucosa playing a key modulatory role at the maternal-fetal interface to support successful pregnancy. Despite having common bone marrow precursors and phenotypic similarities to circulating blood (c) NK cells found in the lymphoid organs and other mucosa, research has established that uNK cells in the uterine mucosa are a pregnancy-specific subset of NK cells. The ontogeny and phenotype of uNK cells inevitably raises the question of what role an innate immune effector cell containing a full set of cytolytic mediators plays in pregnancy. Extensive contributions from several laboratories have confirmed that human and mice uNK cells produce cytokines and growth factors for adequate uterine angiogenesis and vascular remodeling, control of placental growth, and maintenance of the decidual reaction to benefit the pregnancy. Undoubtedly, uNK cells are critical but not essential for successful pregnancy. Conversely, the expected cytotoxic activity of uNK cell seems to be suppressed in normal pregnancy, yet experimental approaches in mice points to the ability of these cells to have their inherent cytotoxic innate immune response triggered. Therefore, there is strong evidence to support uNK cell’s “reviled and revered” behavior in pregnancy. However, whether uNK cells dual role in the pregnant uterus is the result of a single multifunctional cell, or multiple uNK cell subsets remains as a challenging question in reproductive immunology.

Keywords: Mouse uNK cell function, Mouse uNK cell phenotype, Mouse uNK cell life-cycle, mesometrial lymphoid aggregate of pregnancy (MLAp), endometrial leukocyte, mesometrial endometrium, reproducitve immunology, uNK cell immunopheno type, immunology of pregnancy, vascular remodeling, spiral artery, pregnancy failure, abortion and preeclampsia.