Uterine natural killer (uNK) cells appear in implantation sites with decidualization. Initially, they are rare, highly proliferative
cells that become abundant by mid?gestation then die abruptly. Steps regulating the cyclic appearance of uNK cells are incompletely defined. Although progesterone (P4) has an essential role, mature uNK cells of women and mice lack progesterone receptors (PR). Immunohistochemical studies suggest mouse PR? uNK cells may co?localize with PR+ stromal cells while human PR? uNK cells co?localize with immature, DC?SIGN+ dendritic cells (DCs). DCs have the potential to produce progesterone?regulated interleukin (IL)?15, a growth factor essential for uNK cells. Since the high affinity IL?15Rαis presented to differentiating NK cells in trans, requiring cell contact, histologically?detected interactions may be of central importance for uNK cell differentiation. Thus, a pregnancy time?course, histological study of uNK cell differentiation and localization was undertaken in PR?LacZ transgenic mice. PR+ cells and uNK cells were co?localized using LacZ histochemisty and Dolichos biflorus (DBA) lectin staining, respectively. UNK cells appeared mesometrially, where PR+ cells were rare, at gestation day 5.5. UNK cells had limited, apparently random contact with PR+ cells throughout pregnancy and never themselves expressed PR. Thus, uNK cell differentiation does not appear to require
contact with PR+ cells. Potential functions of human uNK cells at the fetal maternal interface are not yet clearly established to date, but several hypotheses are being evaluated, including control of extravillous invasion and uterine vascular remodeling, both are pivotal events for the normal process of pregnancy. uNK cells were believed to play a major role in all stages of preeclampsia development through a well?balanced production of pro?inflammatory cytokines and angiogenic factors which could then trigger the maternal disease. However, in the future, further studies are needed to improve our poor understanding of the role of uNK cells in the pathophysiology of preeclampsia.
|