Immune Tolerance Dysfunction in Pregnancy due to Ambient Air Pollution Exposure

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ABSTRACT Exposure of pregnant women to environmental pollution and toxicants significantly increase risks to mother’s health after birth. Specifically, pollution is association with increased rates of maternal mortality and morbidities of infertility, spontaneous preterm birth, asthma, allergy, cardiovascular disease, autoimmune disease, as well as pre-eclampsia and eclampsia. The maternal immune system plays a critical role in establishing, maintaining, and completing a healthy pregnancy and the constant state of growth and proliferation of this system makes it sensitive to pollutants. Insufficient immunological adaption in pregnancy is associated with many diseases during and after pregnancy. Although epidemiologic studies point to links between specific environmental toxicants and adverse outcomes in mothers, to date, there have been little to no studies of the effects of air pollution toxicants on pregnant mothers’ immune health during and after pregnancy. We hypothesize that chronic exposure to ambient air pollution, specifically fine particulate matter PM2.5, will increase immune dysregulation in pregnant women during, and in short- (immediate postpartum, 1 yr after birth) and long-term periods (3 years after birth) after pregnancy. Using previously collected biosamples from pregnant (n=200) and nonpregnant (n=200) women exposed to high and low levels of pollution (chiefly PM2.5), we will 1) test whether immune cell subsets are different in identity and function in pregnant vs. non pregnant women exposed to high vs. low pollution; 2) identify and validate epigenetic molecular mechanisms driving immune dysfunction in pregnancy vs no pregnancy with high vs low PM2.5 exposure using methylation, EpiTOF, ATAC-seq, and histone ChIP-seq; and 3) map T cell receptor diversity to immune dysfunction in pregnancy vs non pregnancy with high vs. low PM2.5 exposure. If the aims are met, this study will allow us to identify the drivers of immune dysfunction and potential modifiable factors for the future. We will explore how these immune findings are associated with the outcomes of diseases for which we have previously collected metadata: asthma, infections, allergy, pre-eclampsia, eclampsia, preterm birth, and autoimmune disease. Most importantly, our findings will likely impact public health and policy decisions surrounding air pollution exposure in a highly vulnerable population such as pregnant women.