Impact of benzene-induced MIA on fetal T cell development

苯诱导的 MIA 对胎儿 T 细胞发育的影响

• 批准号: 10605881
• 负责人: GIL G MOR
• 金额: $ 38.71万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-13 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605881
• 关键词: 2019-nCoV; Abbreviations; Address; Affect; Air Pollutants; Air Pollution; Area; Asthma; B-Lymphocytes; Benzene; Biological; Child; Chronic Disease; Cities; Clinical; Communicable Diseases; Decidua; Development; Ebola; Equilibrium; Exposure to; Fetal Development; Fetal Growth Retardation; Fetal health; Fetus; Future; Growth and Development function; Health; Homing; Immune; Immune response; Immune system; Incidence; Industrialization; Infant; Infection; Inflammation; Inflammatory; Life; Link; Liver; Maternal Exposure; Modeling; Modification; Molecular; Nature; Neonatal; Outcome; Outcome Study; Pathogenesis; Phenotype; Placenta; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Complications; Premature Birth; Process; Property; Resolution; Severities; Signal Pathway; Signal Transduction; Site; Soil; Superfund; T cell differentiation; T-Cell Development; T-Lymphocyte; Testing; Thymocyte Development; Thymus Gland; Toluene; Training; Vaccines; Viral Respiratory Tract Infection; Volatilization; Xylene; ZIKA; epidemiology study; ethylbenzene; fetal; fetal programming; ground water; immune activation; implantation; in utero; male; maternal morbidity; maternal outcome; microbial; mortality; neonatal morbidity; neonate; offspring; pandemic disease; pathogen; postnatal; preclinical study; prenatal exposure; prevent; public health relevance; response; stressor; vapor intrusion; volatile organic compound

Growing evidences suggests that exposure to volatile, very volatile, and semi-volatile organic compounds (collectively abbreviated VOCs) during vulnerable life windows of susceptibility is an important determinant of maternal-fetal health, with implications for preterm birth, children sensitivity to infections, asthma and other adverse health outcomes. The central theme of this application focuses on deciphering the signaling pathways by which exposure to VOCs during pregnancy have an impact on early life growth and development with a focus on the fetal immune system. Our central hypothesis is that inflammation in the placenta and decidua due to maternal exposure to VOCs, alters the programming of the fetal immune system, which results in an aberrant post-natal immune response to respiratory viral infections. Our preliminary studies suggest that although the fetus may be protected against microbial infection, the outcome of maternal exposure, protective or deleterious, depends on the nature of the immune response and the severity of the inflammatory process at the implantation site (placenta-decidua interface). The mechanisms underlying the response of the fetal immune system and how indirect training by the maternal inflammation takes place is unclear and understudied. Our specific aims are: Aim 1. To determine the effect of VOCs maternal exposure on placental and fetal inflammation. Aim 2. To determine the impact of VOCs exposure on TLR signaling responsible for the homing and differentiation of T and B cells. Aim 3. Characterize the signals from the placenta responsible for the susceptibility to respiratory viral infections of the offspring. Upon completion of these aims we will have a better understanding of the outcomes associated with the impact of VOCs exposure on the placental/decidua unit and its consequent influence on fetal programing and its potential effects on the development of an appropriate neonatal immune responses. Adequate response to infection is the result of a delicate balance between an efficient immune response against pathogens and its quick resolution preventing widespread over-activation. The cellular and molecular components of this regulatory balance are determined during fetal development.

越来越多的证据表明，暴露于挥发性，非常挥发性和半挥发性有机化合物 （统称缩写的VOC）在易感性的生活窗口中，是一个重要的决定因素 产妇健康，对早产，儿童对感染的敏感性，哮喘和其他 不利的健康结果。该应用程序的中心主题着重于解密信号通路 怀孕期间接触VOC的情况会影响早期生活的增长和发展 专注于胎儿免疫系统。我们的中心假设是胎盘和Decidua的炎症 由于母亲接触VOC，改变了胎儿免疫系统的编程，这导致 在对呼吸道病毒感染的异常产后免疫反应中。我们的初步研究 表明尽管胎儿可能受到微生物感染的保护，但母亲的结果 暴露，保护性或有害的，取决于免疫反应的性质和严重程度 植入部位的炎症过程（胎盘 - decidua界面）。依据的机制 胎儿免疫系统的反应以及母体炎症发生的间接训练是如何的 不清楚和研究。我们的具体目的是： 目的1。确定VOC的孕产妇暴露对胎盘和胎儿炎症的影响。 目的2。确定voc的影响对负责归宿的TLR信号的影响 T和B细胞的分化。 AIM 3。表征来自胎盘的信号，负责呼吸病毒的易感性 后代感染。 完成这些目标后，我们将更好地了解与之相关的结果 VOC曝光对胎盘/DECIDUA单元的影响及其对胎儿编程的影响 及其对适当的新生儿免疫反应发展的潜在影响。足够的 对感染的反应是有效的免疫反应之间的微妙平衡的结果 病原体及其快速分辨率阻止了广泛的过度激活。细胞和分子 这种调节平衡的组成部分是在胎儿发育过程中确定的。