Date of Award
Doctor of Philosophy (PhD)
Michal A. Elovitz
The decidua and placenta are immune organs, as most of their functions are mediated by immune cells: implantation, vascular remodeling, and maternal-fetal tolerance. However, how their resident immune cells accomplish each element and promote the growth of a semi-allogeneic fetus is unknown. Research in reproductive immunology has largely focused on the role of systemic maternal T cells in maintaining maternal-fetal tolerance or descriptive studies of the maternal-fetal interface at a single time point in gestation. Furthermore, how these immune cells may contribute to diseases of pregnancy is less understood. The goal of this study is to understand the changes that occur over gestation in the immune populations of the decidua and placenta and how they affect pregnancy outcomes. In humans, these organs are only available for research at two time points: early in gestation after a spontaneous or elective abortion, or postpartum after the massive physiologic change of parturition. As such, we utilize three mouse models of common pregnancy outcomes: (1) parturition, (2) intrauterine fetal demise (IUFD), and (3) fetal neuronal injury. In each model, extensive flow cytometry was completed to characterize alterations in immune composition and function both systemically and at the maternal-fetal interface, in addition to other experimental tools. We find that term parturition involves a loss of immune regulation, and conversely that preterm parturition recruits inflammatory populations. In a model of IUFD, we utilize known information about maternal systemic regulatory T cells (Tregs) to rescue this adverse outcome and then investigate how systemic changes impact the local immune composition using single-cell RNA-sequencing. Finally, using a model of fetal brain injury, we identify a plausible mechanism by which inflammation progresses through tissue compartments at the maternal-fetal interface, ultimately causing pathologic IFN production in the fetal brain. Together these findings demonstrate the diverse roles of the immune populations in the decidua and placenta, and their impact on perinatal outcomes.
Lewis, Emma L., "Immune Modulation At The Maternal-Fetal Interface Regulates Perinatal Outcomes" (2021). Publicly Accessible Penn Dissertations. 4686.
Allergy and Immunology Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons