Uterine natural killer cells: To protect and to nurture

Abstract

During the course of pregnancy, the maternal-fetal interface is tightly regulated and undergoes dynamic changes that promote the successful development of the semi-allogeneic fetus. In response to embryo implantation, the uterus remodels with maternal immune cells occupying the maternal-fetal interface and uterine natural killer (uNK) cells becoming the most prominent leukocyte. Recently, uNK cells have been discovered to be heterogeneous, including conventional NK (cNK) and tissue-resident NK (trNK) cells. Here, we will review the recent advances in uNK cell biology and discuss their functional mechanisms which protect and nurture the growing fetus.

Uterine Natural Killer Cell Heterogeneity: Lessons From Mouse Models

“…We recently used the parabiosis model together with experimentallyinduced decidualization to study early pregnancy events and demonstrated that trNK cells do not circulate. Rather, trNK cells proliferate locally and expand the uNK cell pool with minimal cNK cells contributions (13,27). These data support a two-wave hypothesis for uNK cell accumulation during typical pregnancies (13,27,51).…”

“…Rather, trNK cells proliferate locally and expand the uNK cell pool with minimal cNK cells contributions (13,27). These data support a two-wave hypothesis for uNK cell accumulation during typical pregnancies (13,27,51). The first wave involves local proliferation of trNK cells during decidualization; the second wave postulates the accumulation of cNK cells recruited into the decidua basalis during placentation.…”

“…A placenta anchors each conceptus to the uterine wall, is the site of nutrient, gas, and waste exchange, and induces an immune environment that nurtures and protects the fetus (13,14). Placental dysfunction results in human pregnancy complications that associate with long-term health consequences for both mother and baby.…”

Tissue-Resident NK Cells: Development, Maturation, and Clinical Relevance

“…Potentially, the most relevant immune cells during pregnancy are NK cells. In mice, during the non-menstrual period, NK cells make up 30% of endometrial lymphocytes, and this number increases significantly (70% of lymphocytes) during pregnancy and decidualization [ 188 , 189 ]. Almost all the NK cells in the non-pregnant uterus (endometrium) and pregnant uterus (decidua) are CD56 bright [ 31 , 190 ].…”

How I Manage Natural Killer Cell Deficiency

“…These cells are not vestigial and have been sustained through evolution for a variety of reasons [2]. They are postulated to serve relevant roles in reproductive success, surveillance of cancerous cells and control of viral infections [3][4][5][6]. This is supported by strong evidence accumulated in a wide variety of animal models and in select human contexts collected over the nearly 45 years since NK cells were named as such.…”