Marilen Benner

CHAPTER 1 14 Nutrient exchange Protection fetal environment Barrier towards harmful components Selective passage Spiral artery remodeling Decidualized endometrium Myometrium Placenta (Fetal) Uterus (Maternal) Amniotic cavity T h e P l a c e n t a Connecting fetal and maternal circulation Extravillous trophoblast Maternal immune cells Figure 2. Healthy pregnancy depends on a well-formed placenta. It maintains fetal growth by providing the essential connection with the maternal circulation and it creates a protective environment. KNOWN PARTS OF AN UNKNOWN PICTURE For a number of cell subsets, specialized characteristics of uterine immunity are known. Many of these underline the independence of decidual cells from systemic immunity. The most studied cell types in reproductive immunology are NK cells and T cells. NK cells Decidual NK cells (dNK) display functional and phenotypic characteristics different from peripheral blood NK cells (pbNK) (21, 28). The two major subpopulations of NK cells are composed of CD56 dim CD16 + (NKdim) and CD56 bright CD16 - (NKbright) cells. With their task as innate effector cells to eradicate virally infected and tumor cells, NKdim cells dominate the systemic pool of NK cells (~90%). NKdim cells are of potent cytotoxicity, containing many cytolytic granules such as granzymes and perforin (29). In the uterus, these major killers are almost absent where NKbright cells comprise around 90% of the local NK cells (30). NKbright cells are less cytotoxic but mainly secrete immunoregulatory cytokines, such as IL-10, IL-13, granulocyte – macrophage colony-stimulating factor (GM-CSF), interferon (IFN)- γ , and TNF- β (31). Asides from contributing to the local immune environment, dNK cells also directly influence implantation. By secreting angiopoietin (Ang) ‐ 1, Ang ‐ 2, IFN- γ , and vascular endothelial growth factor (VEGF), they loosen vascular smooth muscle cells, and degrade extracellular matrix components (32, 33). Moreover, decidual NK cells enhance trophoblast migration through GM- CSF secretion (34). Both processes facilitate spiral artery remodeling. This leads to the notion