Immunology of placentation in eutherian mammals

• Published in: Nature Reviews: Immunology 2006-08, Vol.6 (8), p.584-594
• Main Authors: Moffett, Ashley, Loke, Charlie
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Eggs; Female; Fetuses; HLA Antigens - immunology; Humans; Immune response; Immunology; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Laboratory animals; Mammals - embryology; Mammals - immunology; Marsupials; Placenta; Placentation - immunology; Placentation - physiology; Pregnancy; Reptiles & amphibians; review-article; Trophoblasts - cytology; Trophoblasts - immunology; Trophoblasts - physiology; Uterus; Uterus - cytology; Uterus - immunology; Uterus - physiology
• ISSN: 1474-1733; 1474-1741; 1365-2567
• DOI: 10.1038/nri1897

Key Points The anatomical relationship between the placenta and the uterus holds the key to our understanding of the 'immunological paradox' of pregnancy because this is where direct tissue contact occurs. There is great diversity in placental structures in eutherian mammals. For immunologists, the most important feature is the extent to which the placental trophoblast cells invade the uterus. This ranges from no invasion at all (epitheliochorial placentation) to very extensive invasion (haemochorial placentation). The human placenta is the most invasive of all. During pregnancy, in invasive forms of placentation, the uterine lining is transformed into decidual tissue. The most obvious feature of the decidua is the influx of a distinctive population of uterine natural killer (NK) cells. Trophoblast cells express an array of MHC molecules some of which might be potential ligands for receptors expressed by the NK cells (CD94–NKG2A and KIRs (killer-cell immunoglobulin-like receptors)) and expressed by myelomonocytic cells (LILRB1 (leukocyte immunoglobulin-like receptor B1) and LILRB2) in the uterus. Interaction between HLA-C expressed by trophoblast cells and KIRs on maternal NK cells influences reproductive performance. Binding of HLA-G to LILRB molecules might induce tolerance in maternal T cells, thereby allowing cooperation between the innate and adaptive immune systems in mammalian reproduction. It is proposed that the function of uterine NK cells is to alter the structure of the uterine spiral arteries that supply the feto-placental unit. This effect could be mediated directly by affecting the structure or function of the vessel wall (as in mice) or indirectly through the influence on trophoblast-cell infiltration. The arterial modification is necessary to allow sufficient blood flow to the placenta and fetus. Inadequate arterial transformation results in pregnancy disorders (such as fetal growth restriction or pre-eclampsia). A new way to view the immunology of pregnancy is discussed, which takes into account the differing placental strategies used by eutherian mammals. Why some human pregnancies fail might depend on the degree of invasion of the uterus by placental trophoblast cells. The traditional way to study the immunology of pregnancy follows the classical transplantation model, which views the fetus as an allograft. A more recent approach, which is the subject of this Review, focuses on the unique, local uterine immune response to the implanting