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Placental Expression of Interferon- (IFN-) and Its Receptor IFN-R2 Fail to Switch from Early Hypoxic to Late Normotensive Development in Preeclampsia

Harris Birthright Research Center for Fetal Medicine (S.B., A.S., A.E.C., A.P., S.C., K.N.) and Department of Pathology (J.M.), King’s College Hospital Medical School, London SE5 9RS, United Kingdom

Address all correspondence and requests for reprints to: Dr. Subhasis Banerjee, Harris Birthright Research Center for Fetal Medicine, King’s College Hospital Medical School, Denmark Hill, London SE5 9RS, United Kingdom. E-mail: dr_sbanerjee{at}hotmail.com.

The inability of the mother to switch from T helper cell type 1 (Th1) to Th2 cytokine profiles at the fetal-maternal interface has been proposed as one of the primary causes of miscarriage, intrauterine growth restriction (IUGR), and preeclampsia (PE). The Th1 [interferon- (IFN-), TNF-, and IL-12] and Th2 (IL-4 and IL-10) cytokines have opposite effects on human pregnancy. Leukemia inhibitory factor (LIF) promotes embryo implantation and sustains pregnancy, whereas IFN- and TNF- are detrimental to pregnancy. Both IFN- and LIF are produced by maternal cells and tissues at the fetal-maternal interface, whereas the IFN- receptors (IFN-R1 and IFN-R2) and LIF receptor are abundantly expressed on the surface of placental trophoblasts. The effect of IFN- on T lymphocyte activation is influenced by the relative membrane density of its two receptors, particularly IFN-R2. In this study we report that in PE (25–40 wk gestation) and PE complicated by IUGR, IFN-R2 protein expression is severely down-regulated and is similar to that observed in early placenta (7–10 wk gestation) developing under low O₂ tension. IFN- production was found to be inversely related to the IFN-R2 protein expression, and LIF receptor protein expression in PE mimicked that in early placental development. These results show that in PE, placental trophoblasts fail to establish an early to late switch with respect to IFN- and IFN-R2 expression. This supports the hypothesis that trophoblasts control the polarization of maternal immune effectors and cytokine profiles at the fetal-maternal interface that could be subject to oxidative stress in PE.

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