Long-term effects of developmental exposure to a mixture of thyroid disruptors associated with hydrofracking on T cell development and antimicrobial immunity

发育暴露于与水力压裂相关的甲状腺干扰物混合物对 T 细胞发育和抗菌免疫的长期影响

基本信息

  • 批准号:
    10214619
  • 负责人:
  • 金额:
    $ 19.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-13 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

This exploratory research proposal addresses growing concerns about the threats of endocrine disruptor (EDC) water pollutants released during unconventional oil and gas extraction (UOG) to human health. Specifically, these studies focus on how a mixture of 4 UOG chemicals with thyroid hormone (TH) disrupting activity affect the immune system, for which there is no systematic assessment to date. We have developed a reliable, sensitive and cost-effective model system in the amphibian Xenopus that is uniquely suited to investigate the effects of early life exposure to waterborne mixtures of UOG toxicants on immunity later in life. We propose a comparative biology approach in Xenopus to define how postembryonic exposure to a representative mixture of UOG water contaminants with TH activity impacts T cell development and weaken antimicrobial immune response later in life. Our rationale is that (1) a mixture of several EDCs acting toward one hormone axis will allow us to address cellular mechanism leading to acute and persistent effects of this mixture of chemicals on T cell development and function; (2) Although TH axis affects the immune system, little is still known about the long-term biological impacts of TH disruptors on immunity; and (3) Xenopus is a reliable, extensively characterized and widely recognized model of human perinatal endocrinology and biomedical research on the TH axis, including dependence of TH signaling for the differentiation of adult-type T cell immunity during metamorphosis. Other features advantageous for achieving our goal are the external development of tadpoles, which are free of maternal influence and easily accessible to exposure during postembryonic development, and the cost effectiveness of exposing tadpoles in large numbers to EDCs. To test the hypothesis that developmental exposure to a mixture of TH-disruptors associated with UOG alters T cell development, resulting in long-term perturbation of immune homeostasis and poorer antimicrobial immunity, we will determine: (1) acute effects of UOG-EDCs on tadpole T cell differentiation and immune homeostasis , by defining the impact of tadpole exposure on homeostatic lymphocyte populations using flow cytometry, histology and transcriptomics; (2) long-term effects on immune homeostasis and anti-microbial immunity of developmental exposure to a mixture of TH-disruptors persisting after metamorphosis , by measuring changes at steady state and in response to the ranavirus FV3 (similar to poxviruses such as vaccinia, a strong CD8 T cell inducer) and Mycobacterium marinum (a pathogen of frogs and humans, a strong CD4 T cell inducer); and (3) TH-disruptor activity of each of the 4 UOG-EDC alone and their potential additive and synergistic actions. Innovative convergent findings from infection with two different types of pathogens (pox-like FV3 and Mycobacteria) in Xenopus whose TH axis and immune system are remarkably conserved with those of mammals will provide novel and compelling evidence regarding effects of UOG-EDCs on the immune system function relevant to human health.

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

暂无数据

数据更新时间:2024-06-01

JACQUES Robert的其他基金

Long-term effects of developmental exposure to a mixture of thyroid disruptors associated with hydrofracking on T cell development and antimicrobial immunity
发育暴露于与水力压裂相关的甲状腺干扰物混合物对 T 细胞发育和抗菌免疫的长期影响
  • 批准号:
    9977347
    9977347
  • 财政年份:
    2020
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
University of Rochester Medical Center PREP Training Program
罗切斯特大学医学中心 PREP 培训计划
  • 批准号:
    10685490
    10685490
  • 财政年份:
    2020
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
University of Rochester Medical Center PREP Training Program
罗切斯特大学医学中心 PREP 培训计划
  • 批准号:
    10267209
    10267209
  • 财政年份:
    2020
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
Involvement of Nonclassical MHC in Early T Cell Ontogeny in Xenopus
非经典 MHC 参与非洲爪蟾早期 T 细胞个体发育
  • 批准号:
    7701182
    7701182
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
爪蟾免疫生物学研究资源
  • 批准号:
    7915154
    7915154
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
爪蟾免疫生物学研究资源
  • 批准号:
    7878392
    7878392
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
爪蟾免疫生物学研究资源
  • 批准号:
    8306997
    8306997
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
爪蟾免疫生物学研究资源
  • 批准号:
    7901454
    7901454
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
ROLE OF NON-CLASSICAL MHC CLASS I AND HSPs IN IMMUNITY
非经典 I 类 MHC 和 HSP 在免疫中的作用
  • 批准号:
    7848035
    7848035
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:
Involvement of Nonclassical MHC in Early T Cell Ontogeny in Xenopus
非经典 MHC 参与非洲爪蟾早期 T 细胞个体发育
  • 批准号:
    7915338
    7915338
  • 财政年份:
    2009
  • 资助金额:
    $ 19.25万
    $ 19.25万
  • 项目类别:

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