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SUMMARY:Mothers' compromise.  How NK cells regulate placentation. - Dr And
 rew Sharkey\, Department of Pathology\, University of Cambridge
DTSTART:20130605T113000Z
DTEND:20130605T123000Z
UID:TALK45003@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Reproductive failure in humans is common.\nNormal fetal growth
  and development depend on increasing uterine blood flow to the feto-place
 ntal unit throughout pregnancy.  In humans\, trophoblast cells from the pl
 acenta invade the uterus and convert the mother’s spiral arteries to hig
 h conductance vessels.  However\, uncontrolled trophoblast penetration of 
 the uterus leads to life-threatening haemorrhage.  Conversely\, when troph
 oblast invades poorly\, the failure to transform spiral arteries leads to 
 inadequate placental perfusion.  Clinically\, this can present as fetal gr
 owth restriction (FGR)\, still-birth\, pre-eclampsia or recurrent spontane
 ous miscarriage.  Thus\, these major pathological disorders of human pregn
 ancy share a common pathogenesis of defective trophoblast invasion. \n\nRe
 gulation of trophoblast invasion by maternal uterine NK cells regulates pl
 acentation.\nThere is now strong evidence that decidual NK cells (dNK)\, a
 s the dominant lymphocyte in the decidua during early pregnancy\, are like
 ly candidates to mediate this delicate negotiation between fetal trophobla
 st cells and maternal decidua to prevent over or under invasion. Specifica
 lly\, we are studying how maternal receptors of the KIR family expressed b
 y dNK\, respond to fetal trophoblast expressing the KIR-ligands\, HLA-C mo
 lecules. Both KIR and HLA-C are polymorphic and genetic studies show mater
 nal KIR/fetal HLA-C combinations that favour inhibition of dNK cell functi
 on are associated with reproductive failure due to defective trophoblast i
 nvasion. Conversely some activating combinations such as KIR2DS1/HLA-C2 ar
 e protective. \n\nWe have now shown that ligation of the activating recept
 or KIR2DS1 on dNK cell clones can alter cytokine production in dNK cells a
 nd promote trophoblast invasion. These results link our genetic findings t
 o functional responses of dNK and show how allorecognition by maternal dNK
  cells may determine successful placentation. \n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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