Aberrant Uterine Natural Killer (NK)-Cell Expression and Altered Placental and Serum Levels of the NK-Cell Promoting Cytokine Interleukin-12 in Pre-Eclampsia

Authors

  • Nora Bachmayer,

    1.  Arrhenius Laboratories for Natural Sciences, Department of Immunology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden;
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  • Rangeen Rafik Hamad,

    1.  Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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  • Lucie Liszka,

    1.  Arrhenius Laboratories for Natural Sciences, Department of Immunology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden;
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  • Katarina Bremme,

    1.  Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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  • Eva Sverremark-Ekström

    1.  Arrhenius Laboratories for Natural Sciences, Department of Immunology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden;
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Nora Bachmayer, Arrhenius laboratory of Natural Sciences F5, The Department of Immunology, The Wenner-Gren Institute, Stockholm University, Svante Arrhenius väg 16-18, 106 91 Stockholm, Sweden.
E-mail: nora.bachmayer@imun.su.se

Abstract

Problem  Natural killer (NK) cells are the most abundant lymphocyte population at the maternal–fetal interface. They are suggested to be important during placentation by controlling trophoblast invasion. If placentation is suboptimal, pre-eclampsia can occur.

Method of study  Decidual NK (dNK) cells were examined at delivery in 46 women, 22 pre-eclamptic women and 24 healthy controls, by staining for CD56 and CD94 with immunohistochemistry (IHC). Furthermore, we investigated the placental expression and the serum levels of the NK-cell activating cytokines interleukin(IL)-12, IL-15, IL-18 and the anti-inflammatory cytokine IL-10 by IHC and enzyme-linked immunosorbent assay (ELISA), respectively.

Results  Pre-eclamptic women had higher number of CD56+ and CD94+ cells in the decidua, indicating an altered receptor expression of dNK cells. We also demonstrate for the first time that the villous trophoblasts show strong immunostaining for IL-12 in placentae from healthy controls, while women suffering from pre-eclampsia have significantly less IL-12. However, pre-eclamptic women had significantly elevated IL-12 and IL-15 levels in serum.

Conclusion  Results show increased numbers and altered phenotype of dNK cells in pre-eclampsia, supporting the importance of these cells for a healthy pregnancy. The altered receptor expression of dNK cells together with diminished placental IL-12 expression could implicate an altered NK cell-regulation in pre-eclampsia.

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