Metabolic Regulation of Immune Cell Function at the Maternal Fetal Interface

/Abstract Metabolic programming and nutrient utilization are increasingly recognized as key determinants of immune cell function. Advances in understanding of immunometabolism have led to important therapeutic applications in oncology and rheumatology. In these diseases, changes in metabolic programming are associated with immune activation or suppression. Despite the critical role of the immune system and the significant maternal metabolic changes that occur during pregnancy, there is limited understanding of immunometabolism at the maternal-fetal interface. Immune cell function is highly dynamic during pregnancy, with pro- and anti- inflammatory phenotypes occurring at different gestational weeks. Our preliminary data demonstrate significant differences in placenta metabolite composition in each trimester. We hypothesize that metabolic changes at the maternal-fetal interface contribute to immune phenotype in pregnancy. The overall goal of this proposal is to examine how nutrient availability and utilization impacts immune cell function at the maternal-fetal interface. Our experiments will assess the combined metabolic and inflammatory phenotypes of immune cells at the single-cell level at each trimester during normal pregnancy. In Aim 1, we will determine the role of glucose utilization in immune cells throughout gestation, while in Aim 2, we will evaluate glutamine metabolism in immune cells during pregnancy. To address these aims, we will use high parameter single-cell flow cytometry assays to determine the metabolic phenotypes of human immune cells from placenta and uterine decidua in each trimester during normal pregnancy. In addition, we will analyze transcriptomics and metabolomics from decidual immune cells to determine how glucose and amino acid metabolism in immune cells changes as pregnancy progresses. Importantly, we will also directly assess potential metabolic drivers of immune cell phenotype with ex vivo stimulation assays to assess mechanism. Our team consists of experts in Maternal Fetal Medicine, Immunology, Metabolism, and -omics including single-cell analysis. This combined expertise as well as access to an extensive pregnancy biorepository containing well characterized placenta and decidual samples throughout gestation ensures that we are well poised to address this critical gap in understanding immunometabolism during pregnancy. Project Number: 1R01HD120335-01 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: STEPHEN McCARTNEY | Institution: UNIVERSITY OF WASHINGTON, SEATTLE, WA | Award Amount: $672,234 | Activity Code: R01 | Study Section: Pregnancy and Neonatology Study Section[PN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11272965