Professor Ashley Moffett
The question we are addressing is that the maternal uterine immune system is crucial in regulating the process of placentation. Specifically, how does the dominant population of uterine leukocytes, Natural Killer (NK) cells recognise MHC Class I ligands on fetal trophoblast cells and how might this result in altered trophoblast function. This view of the maternal-fetal relationship does not consider the placenta as akin to an allograft that must avoid rejection by maternal T cells. Instead, we have defined several molecular recognition systems whereby cells of the innate immune system discern and respond to the placenta.
More recently, we have focused on two trophoblast MHC Class 1 ligands, HLA-G and HLA-C. More than 90% of uterine leukocytes can bind to HLA-G, meaning that this placental molecule may provide a "pregnant" signal to the local immune cells. HLA-C is the only polymorphic trophoblast molecule so far identified. This is the dominant ligand for NK cells in blood but we have increasing evidence that a major function of the NK receptors that bind HLA-C (known as KIR) are pivotal in determining how far trophoblast penetrates into the uterus. This trophoblast invasion is essential to tap into the maternal blood flow. In our immunogenetic studies, the results now emerging show that one particular maternal KIR and fetal HLA-C combination is associated with the major diseases of pregnancy - recurrent miscarriage, fetal growth restriction, pre-eclampsia. The impact of the immunological maternal-fetal interaction on low birth weight has consequences on adult health and so this research will have far-reaching consequences.