HLA-G, pre-eclampsia, immunity and vascular events

Pre-eclampsia, one of the main complications in pregnancy, is characterised by shallow cytotrophoblast invasion of decidua as well as by vascular endothelial cell dysfunction, leading to a poor perfusion of placenta. A striking feature of pre-eclamptic pregnancies is that expression of HLA-G protein is reduced in term placentas compared with normal pregnancy. How such HLA-G deficient expression may be related to the pre-eclamptic pathology is unknown. Here, we review the major structural characteristics of HLA-G and some of its functions that have been recently characterised. Soluble HLA-G1 isoform down-regulates both CD8(+) and CD4(+) T cell reactivity. HLA-G also modulates innate immunity by binding to several NK and/or decidual receptors, inducing particular cytokine secretion. HLA-G was shown to be less susceptible to human cytomegalovirus-derived US protein down-modulation. Finally, soluble HLA-G1 down-regulates endothelial cell proliferation and migration. In view of these different HLA-G properties, we will briefly discuss how defective HLA-G function may contribute to the low trophoblast invasion and vascular abnormalities observed in pre-eclamptic placentas.