The role of uterine natural killer cell-inhibition in pregnancy

Education of natural killer (NK) cells is a genetically determined process that primes NK-cell activity upon the binding of their inhibitory receptors to self-ligands. Although NK-cell education is predictable and measurable in the laboratory, its biological significance is unknown. This thesis shows that the inhibitory NK cell receptor NKG2A protects against the hypertensive disorder of pregnancy pre-eclampsia in individuals genetically programmed to favour the engagement of NKG2A with its ligand HLA-E. Using NKG2A-deficient Klrc1-/- mice, this thesis demonstrates that NKG2A is required to educate uterine NK cells to regulate uterine vascular adaptation to pregnancy, placental function and transcriptome, as well as fetal growth. Immune checkpoint blockade of NKG2A during pregnancy in wild-type mice did not affect fetal growth, suggesting acute ablation of this pathway does not interfere with pregnancy outcome. In addition, generation of a humanised mouse model to test the notion that uterine NK cell inhibition driven by KIR: HLA interactions leads to poor pregnancy outcomes, was attempted.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Shreeve, Norman

Advisor dc:contributor.advisor

• Colucci, Francesco

• Pregnancy
• Uterine NK cells
• NKG2A
• Pre-eclampsia
• FGR

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8d2d5c29-e002-4381-8adb-c676212125ab/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0001-5193-6376

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/319720