Senior Research Associate
The question we are addressing in the Moffett group, to which I belong, 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 extravillous fetal trophoblast cells and how might this result in altered trophoblast function.
HLA-C is the only polymorphic trophoblast molecule so far identified. This is the dominant ligand for NK cells in blood and 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 the interstitial trophoblast penetrates into the uterus. This trophoblast invasion is essential to tap into the maternal blood flow. In the immunogenetic studies that I am involved in, 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.
Funding: Wellcome Trust
Hiby SE, Regan L, Lo W, Farrell L, Carrington M, Moffett A. (2008) Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage. Hum Reprod. 23:972-6
Moffett A, Hiby SE. (2007) How does the maternal immune system contribute to the development of pre-eclampsia? Placenta. 28 Suppl A:S51-6.
Hiby SE, Walker JJ, O?Shaughnessy KM, Redman CWG, Carrington M, Trowsdale J and Moffett A. (2004) Combinations of maternal and paternal KIR and HLA-C genes influence the risk of pre-eclampsia. J Exp Med. 200:957-65.