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The role of uterine natural killer cell-inhibition in pregnancy

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cam.restrictionthesis_access_embargoed
cam.supervisorColucci, Francesco
cam.supervisor.orcidColucci, Francesco [0000-0001-5193-6376]
dc.contributor.authorShreeve, Norman
dc.date.accessioned2021-04-10T22:45:49Z
dc.date.available2021-04-10T22:45:49Z
dc.date.submitted2020-06-04
dc.description.abstractEducation 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.
dc.identifier.doi10.17863/CAM.66841
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/319720
dc.language.isoeng
dc.publisher.institutionUniversity of Cambridge
dc.rightsAll Rights Reserved
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.subjectPregnancy
dc.subjectUterine NK cells
dc.subjectNKG2A
dc.subjectPre-eclampsia
dc.subjectFGR
dc.titleThe role of uterine natural killer cell-inhibition in pregnancy
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.type.qualificationtitlePhD in Reproductive Immunology
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved/
rioxxterms.typeThesis

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Theses - Obstetrics and Gynaecology