Ashley Moffett is available for consultancy.
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 cells recognise MHC Class I ligands on fetal trophoblast cells and how might this result in altered trophoblast function. More recently, we have focused on two trophoblast MHC Class I ligands, HLA-G and HLA-C. There is 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. We have shown that one particular maternal KIR and fetal HLA-C combination is associated with recurrent miscarriage, fetal growth restriction and pre-eclampsia. The impact of the immunological maternal-fetal interaction on low birth weight has far reaching consequences including on adult health.
enzyme assays ; immunohistochemistry ; HLA-C ; KIR ; HLA-G ; human studies ; natural killer cells ; pregnancy ; FACS
Hiby SE, Apps R, Chazara O, Farrell LE, Magnus P, Trogstad L, Gjessing HK,
Carrington M, Moffett A. (2014) Maternal KIR in combination with paternal HLA-C2 regulate human birth weight. J Immunol. 192(11):5069-73.
Moffett A, Colucci F. (2014) Uterine NK cells: active regulators at the maternal-fetal
interface. J Clin Invest. 124(5):1872-9.
Kieckbusch J, Gaynor LM, Moffett A, Colucci F. (2014) MHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual vascular remodelling.
Nat Commun 5:3359.
Nakimuli A, Chazara O, Byamugisha J, Elliott AM, Kaleebu P, Mirembe F,
Moffett A. (2014) Pre-eclampsia, pregnancy and parturition in women of African ancestry. American Journal of Obstetrics and Gynecology 210(6):510-520.
Nakimuli A, Elliott AM, Kaleebu P, Moffett A, Mirembe F. (2013)
Hypertension persisting after pre-eclampsia: a prospective cohort study at
Mulago Hospital, Uganda. PLoS One Dec 31
Apps R, Qi Y, Carlson JM, Chen H, Gao X, Thomas R, Yuki Y, Del Prete GQ,
Goulder P, Brumme ZL, Brumme CJ, John M, Mallal S, Nelson G, Bosch R,
Heckerman D, Stein JL, Soderberg KA, Moody MA, Denny TN, Zeng X, Fang J,
Moffett A, Lifson JD, Goedert JJ, Buchbinder S, Kirk GD, Fellay J, McLaren P,
Deeks SG, Pereyra F, Walker B, Michael NL, Weintrob A, Wolinsky S, Liao W,
Carrington M. (2013) Influence of HLA-C expression level on HIV control.
Parham P, Moffett A. (2013) Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution. Nat Rev Immunol. 13(2):133-44.
Wilkens J, Male V, Ghazal P, Forster T, Gibson DA, Williams AR, Brito-Mutunayagam
SL, Craigon M, Lourenco P, Cameron IT, Chwalisz K, Moffett A*, Critchley HO*.
*Joint senior authors. (2013) Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.
J. Immunology 191(5):2226-35.
Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M, (2011) Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci USA. 108: 4012-4017
Male V, Sharkey A, Masters L, Kennedy PR, Farrell LE, Moffett A. (2011) The effect of pregnancy on the uterine NK cell KIR repertoire. Eur J Immunol. 41(10):3017-27.
Colucci F, Boulenouar S, Kieckbusch J, Moffett A. (2011) How does variability of immune system genes affect placentation? Placenta 32: 539-545
Apps R, Sharkey A, Gardner L, Male V, Trotter M, Miller M, North R, Founds S and Moffett A. (2011) Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells. Placenta Jan;32(1):33-43.
Hiby SE, Apps R, Sharkey AM, Farrell LE, Gardner L, Mulder A, Claas FH, Walker JJ, Redman CC, Morgan L, Tower C, Regan L, Moore GE, Carrington M, Moffett A. (2010) Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2. J. Clin. Invest. 120: 4102-4110.
Male V, Hughes T, McClory S, Colucci F, Caligiuri MA, Moffett A (2010). Immature NK cells, capable of producing IL-22, are present in human uterine mucosa. J. Immunol. 185: 3913-3918.