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: 10626886
• 负责人: Kari C. Nadeau
• 金额: $ 42.88万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 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 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626886
• 关键词: ATAC-seq; 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; Histones; Hypersensitivity; IL27RA gene; 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; Proliferating; Proteomics; Public Health; Public Policy; 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; absorption; adverse outcome; ambient air pollution; cohort; epidemiology study; fine particles; health of the mother; healthy pregnancy; high dimensionality; high risk; immune health; innovative technologies; maternal immune system; maternal morbidity; parous; phenotypic biomarker; pollutant; post pregnancy; 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.

摘要 孕妇暴露于环境污染和有毒物质会大大增加母亲的风险。 出生后的健康具体而言，污染与产妇死亡率和发病率的增加有关 不孕症，自发性早产，哮喘，过敏，心血管疾病，自身免疫性疾病，以及 先兆子痫和子痫母体免疫系统在建立， 保持，并完成健康的怀孕和不断的增长和增殖的状态， 系统对污染物敏感。妊娠期免疫适应不足与 怀孕期间和怀孕后的许多疾病。尽管流行病学研究指出， 环境毒物和母亲的不良后果，迄今为止，很少或没有研究， 大气污染毒物对孕妇孕期及产后免疫健康的影响我们 假设长期暴露于环境空气污染，特别是细颗粒物PM2.5， 在怀孕期间和短期内（产后即刻，产后1年）增加孕妇的免疫失调 出生后）和怀孕后的长期（出生后3年）。使用之前收集的生物样本， 孕妇（n=200）和非孕妇（n=200）暴露于高水平和低水平污染（主要是PM2.5）， 我们将1）测试免疫细胞亚群在妊娠与非妊娠中的身份和功能是否不同 暴露于高污染与低污染的妇女; 2）确定和验证表观遗传分子机制， 使用甲基化，在高与低PM2.5暴露下怀孕与未怀孕的免疫功能障碍， EpiTOF、ATAC-seq和组蛋白ChIP-seq;和3）将T细胞受体多样性映射到免疫功能障碍， 怀孕与非怀孕，高与低PM2.5暴露。如果目标实现，这项研究将使我们能够 确定免疫功能障碍的驱动因素和未来潜在的可改变因素。我们将探讨如何 这些免疫发现与我们先前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 重要的是，我们的发现可能会影响公众健康和有关空气污染暴露的政策决定 尤其是孕妇等高危人群。