The human uterine endometrium harbors various immune cell populations including NK cells, macrophages, T cells, B cells and neutrophils (1
). Endometrial NK cells (eNK) increase in number after ovulation becoming the major endometrial immune cell type. With menstruation, shedding of the uterine mucosa carries with it most of the endometrial immune cells. However if pregnancy takes place, NK cells continue to accumulate becoming 70% of the lymphocytes in the human decidua by the end of the first trimester of gestation (3
). We refer to these as decidual NK cells (dNK).
Human dNK cells have been fully characterized. Their gene expression profile sets them apart from the two main peripheral blood NK cell (pNK) subsets (4
). Like CD56dim
pNK cells dNK cells are granular and express killer cell immunoglobulin like receptors (KIR) (5
). However they lack cytotoxic activity and expression of CD16 (4
) as does the minor CD56bright
pNK subset. dNK cells produce a number of immunosuppressive molecules that may contribute to the establishment of maternal-fetal immune tolerance (4
). Their activation also leads to the secretion of proinflammatory, angiogenic and trophoblast migration promoting factors and thus it was proposed that they may play a role in invasion of the endometrium during implantation and placental vascular remodeling during early pregnancy (9
Unlike dNK and pNK cells, characterization of eNK cells is limited. They share many properties with dNK cells such as CD9 expression, the level of CD56 expression, absence of CD16 expression, granularity and lack of cytotoxic activity (2
), and therefore they have been thought of as equivalent to dNK cells. More recently an analysis of eNK cells was reported (13
). Phenotypic comparison to previously published data on dNK cells revealed some phenotypic differences. Unlike fresh dNK cells, freshly isolated eNK cells were reported not to express the activating receptor NKp30, and failed to secrete the angiogenic cytokine VEGF and placental growth factor (13
). However no direct comparison of dNK and eNK cells was provided.
Here we present a genome wide expression profile comparison of the dNK and eNK cell populations. The analysis reveals that dNK and eNK are two distinct NK cell subtypes, as different as CD56bright and CD56dim pNK cells.