Immune Tolerance Dysfunction in Pregnancy due to Ambient Air Pollution Exposure

由于环境空气污染暴露而导致妊娠期免疫耐受功能障碍

• 批准号: 10225619
• 负责人: Kari C. Nadeau
• 金额: $ 37.68万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10225619
• 关键词: ATAC-seq; Address; Affect; Age; Air Pollution; Area; Asthma; Autoimmune Diseases; Automobile Driving; Bioinformatics; Birth; Blood; Blood specimen; Cardiovascular Diseases; Cells; ChIP-seq; Chronic; Clinical; Data; Data Set; Discipline of obstetrics; Disease; Disease Outcome; Eclampsia; Environmental Pollution; Epigenetic Process; Experimental Designs; Exposure to; Female; Fetus; Functional disorder; Funding; Future; Gene Expression; Growth; Health Policy; Histones; Hypersensitivity; Immune; Immune System Diseases; Immune Tolerance; Immune response; Immune system; Immunologics; Immunology; Immunosuppression; Individual; Infection; Infertility; Knowledge; Link; Long-Term Effects; Lung; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Maternal Mortality; Measures; Metadata; Methods; Methylation; Modification; Molecular; Mothers; National Institute of Environmental Health Sciences; Outcome; Particulate Matter; Plasma; Play; Pollution; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Trimesters; Pregnant Women; Premature Birth; Proteomics; Public Health; Publishing; Regulatory T-Lymphocyte; Research; Research Project Grants; Risk; Role; Sampling; Second Pregnancy Trimester; Stream; System; T cell receptor repertoire sequencing; T-Cell Receptor; T-Lymphocyte; Testing; Time; Toxic Environmental Substances; Toxicant exposure; Vulnerable Populations; Woman; Women' s Health; adverse outcome; ambient air pollution; cohort; cytokine; epidemiology study; fine particles; health of the mother; healthy pregnancy; high dimensionality; high risk; immune health; innovative technologies; maternal morbidity; phenotypic biomarker; pollutant; pregnant; response; tool; toxicant

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.

抽象的 孕妇接触环境污染和有毒物质会显着增加母亲的风险 具体而言，污染与孕产妇死亡率和发病率上升有关。 不孕症、自发性早产、哮喘、过敏、心血管疾病、自身免疫性疾病等 如先兆子痫和子痫，母体免疫系统在建立、 维持并完成健康妊娠以及其持续的生长和增殖状态 系统使其对污染物敏感与妊娠期免疫适应不足有关。 尽管流行病学研究指出了怀孕期间和怀孕后的许多疾病之间的联系。 环境毒物和母亲的不良后果，迄今为止，几乎没有研究 空气污染有毒物质对孕妇怀孕期间和怀孕后免疫健康的影响。 长期暴露于环境空气污染，特别是细颗粒物 PM2.5 中，会 增加孕妇在产期间和短期内（产后即刻、产后 1 年）的免疫失调 出生）和怀孕后的长期（出生后 3 年）使用以前收集的生物样本。 暴露于高水平和低水平污染（主要是 PM2.5）的怀孕（n=200）和非怀孕（n=200）女性， 我们将 1) 测试免疫，怀孕与非怀孕的细胞亚群在身份和功能上是否不同 2）识别并验证表观遗传驱动的分子机制 使用甲基化技术，在高 PM2.5 暴露与低 PM2.5 暴露情况下，妊娠期与未妊娠期的免疫功能障碍， EpiTOF、ATAC-seq 和组蛋白 ChIP-seq；3) 将 T 细胞受体多样性映射到免疫功能障碍 怀孕与未怀孕的 PM2.5 暴露量高与低的比较 如果目标得以实现，这项研究将使我们能够做到这一点。 我们将探讨如何确定免疫功能障碍的驱动因素和未来潜在的可改变因素。 这些免疫发现与我们之前收集的疾病的结果相关 元数据：哮喘、感染、过敏、先兆子痫、子痫、早产和自身免疫性疾病。 重要的是，我们的研究结果可能会影响公众健康和有关空气污染暴露的政策决策 孕妇等高度脆弱人群。