Natural Killer cells play an important role in the development of the placenta during the early stages of pregnancy. The mechanism of angiogenesis is controlled in part by the effect of uterine natural killer cells (uNK) and their production of cytokines. The mechanisms and role of the uNK cells will be examined and the importance of the uNK cells become clear when disorders relating to dysfunctional NK cells are examined.
Peripheral Natural Killer Cells:
Natural killer (NK) cells are lymphocytes that are part of the innate immune system and have different functions depending on their location. Peripheral NK (pNK) cells recognise MHC class 1 molecules on the surface of stressed cells. There are two phenotypes of pNK cells. CD56dim CD16+ NK cells make up 90% of the pNK cell population and have cytotoxic tendencies, whereas CD56bright CD16- cells are less cytotoxic but produce the majority of cytokines that are important for immunological regulation and make up 10%. The presence of receptors on the surface of the NK cells contributes to their function (table 1).
Uterine Natural Killer Cells:
uNK cells, also known as decidual NK (dNK) cells are present in the decidua, which is the lining of the uterus. This lining is in close contact with fetal trophoblast cells (Fig. 1) and is necessary to separate the fetus from the maternal circulatory system. uNK cells have the CD56bright CD16- phenotype, so are similar to the less cytotoxic pNK cells. Research by Spornitz (1992) showed that uNK cells have different stages of growth (Fig. 2) and that their numbers decline dramatically after the first trimester. The origin of uNK cells has been debated and different theories have been suggested. Yamaguchi et al. (2006) suggest that peripheral CD56bright NK cells may migrate into the uterus using L-selectin for recruitment, and then proliferate by undergoing specific differentiation. This is supported by Hanna et al (2003) who showed that receptors on the CD56bright CD16- pNK cells, of which most are also found on dNK cells, are important in NK cell migration. However, other research has found that uNK cells actually originate from CD56dim CD16+ pNK cells (Keskin et al. 2003); Manaster and
Mandelboim (2010) propose that the origin may be a combination of both and Table 1 supports this as the uNK cells have similarities with both pNK cell types.
In order for a pregnancy to be successful, there needs to be a sustainable flow from the maternal blood to fetal blood via spiral arteries; these form the connection between maternal blood and the placenta. In order for this to occur, there needs to be remodeling of uterine arteries. This occurs when extravillous trophoblasts (EVTs) penetrate through the endometrium and some of the myometrium (Fig. 1) during early pregnancy (Jauniaux et al. 2003). uNK cells play an important part in trophoblast migration and also in vascular remodeling, where the smooth muscle walls of...