Date of Award

2022

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Natural Killer (NK) cells are abundant in pregnancy and contribute to the health of the fetus. Uterine NK (uNK) cells provide less cytotoxic function than their conventional NK (cNK) cell counterparts. Various combinations of Killer Immunoglobulin Receptor (KIR)- Human Leukocyte Antigen (HLA) on maternal NK and fetally derived cells, respectively, can have different effects on the health of pregnancy in humans. Murine NK cells contain Ly49 receptors, an equivalent to KIRs. Therefore, Ly49 receptor interactions with fetally-derived MHC-I molecules can be a valuable model for studying the role of NK cells in pregnancy. The process of spiral artery remodeling can indicate the health of a pregnancy, as it allows for placental perfusion and increased blood flow to the fetus. Previous studies have shown that allogeneic MHC molecules produce suboptimal spiral artery remodeling, a process characterized by reduced interferon gamma (IFN-γ) production and decreased fetal weights. Ly49 knockout mice have been derived on a B6 background. Litters from these mice have decreased fetal weights especially when fetally derived cells carry foreign MHC molecules. Ly49 knockout mice have defects in IFN-γ production and spiral artery remodeling, indicating that Ly49 receptors on NK cells at the maternal-fetal interface are important for the production of IFN-γ that is necessary for spiral artery remodeling. Understanding of the mechanisms used by Ly49 receptors on uNK cells during pregnancy will allow for the potential discovery of therapeutics for women with high-risk pregnancies such as recurrent miscarriage and preeclampsia.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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