University of Cambridge > Talks.cam > Immunology in Pathology > Mothers' compromise. How NK cells regulate placentation.

Mothers' compromise. How NK cells regulate placentation.

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Host: Jim Kaufman (jfk31@cam.ac.uk)

Reproductive failure in humans is common. Normal fetal growth and development depend on increasing uterine blood flow to the feto-placental unit throughout pregnancy. In humans, trophoblast cells from the placenta invade the uterus and convert the mother’s spiral arteries to high conductance vessels. However, uncontrolled trophoblast penetration of the uterus leads to life-threatening haemorrhage. Conversely, when trophoblast invades poorly, the failure to transform spiral arteries leads to inadequate placental perfusion. Clinically, this can present as fetal growth restriction (FGR), still-birth, pre-eclampsia or recurrent spontaneous miscarriage. Thus, these major pathological disorders of human pregnancy share a common pathogenesis of defective trophoblast invasion.

Regulation of trophoblast invasion by maternal uterine NK cells regulates placentation. There is now strong evidence that decidual NK cells (dNK), as the dominant lymphocyte in the decidua during early pregnancy, are likely candidates to mediate this delicate negotiation between fetal trophoblast cells and maternal decidua to prevent over or under invasion. Specifically, we are studying how maternal receptors of the KIR family expressed by dNK, respond to fetal trophoblast expressing the KIR -ligands, HLA -C molecules. Both KIR and HLA -C are polymorphic and genetic studies show maternal KIR /fetal HLA -C combinations that favour inhibition of dNK cell function are associated with reproductive failure due to defective trophoblast invasion. Conversely some activating combinations such as KIR2DS1 /HLA-C2 are protective.

We have now shown that ligation of the activating receptor KIR2DS1 on dNK cell clones can alter cytokine production in dNK cells and promote trophoblast invasion. These results link our genetic findings to functional responses of dNK and show how allorecognition by maternal dNK cells may determine successful placentation.

This talk is part of the Immunology in Pathology series.

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