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 孕妇暴露于环境污染和毒物中，大大增加了母亲的风险 出生后的健康。具体而言，污染是与孕产妇死亡率增加的相关性 不育，自发性早产，哮喘，过敏，心血管疾病，自身免疫性疾病 作为子痫前期和eClampsia。孕产妇免疫系统在建立， 维持并完成健康怀孕以及持续的生长状态和增殖状态 系统使其对污染物敏感。怀孕的免疫适应不足与 怀孕期间和之后的许多疾病。尽管流行病学研究指出了特定之间的联系 到目前为止 空气污染有毒物质对怀孕期间和之后怀孕母亲的免疫健康的影响。我们 假设长期暴露于环境空气污染，特别是精细的特定物质PM2.5 增加在孕妇和短暂的孕妇的免疫失调（产后立即，1年后1年 生日）和长期（出生后3年）怀孕后。使用先前收集的生物样本 怀孕（n = 200）和非怀孕（n = 200）妇女受到高水平和低污染的妇女（主要是PM2.5）， 我们将1）测试免疫小球子集的身份和功能是否不同 妇女暴露于高污染和低污染； 2）识别和验证表观遗传分子机制驱动 妊娠中的免疫功能障碍与没有怀孕，高pm2.5使用甲基化暴露， Eptof，Atac-Seq和Hisstone Chip-Seq； 3）将T细胞受体多样性映射到免疫功能障碍 怀孕与非妊娠，高pm2.5暴露。如果达到目标，这项研究将使我们能够 确定未来的免疫功能障碍的驱动因素和潜在的可修改因素。我们将探讨如何 这些免疫发现与我们先前已收集的疾病结果有关 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。最多 重要的是，我们的发现可能会影响围绕空气污染暴露的公共卫生和政策决策 在高度脆弱的人群中，例如孕妇。