Novel mechanisms of immunological priming after circadian disruption

昼夜节律破坏后免疫启动的新机制

基本信息

  • 批准号:
    9187015
  • 负责人:
  • 金额:
    $ 35.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-01-15 至 2018-11-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Shift workers comprise nearly 20% of the US working population, and exhibit disparately high rates of several cancers, obesity, diabetes, stroke, and circulatory disease. A better understanding of the mechanistic factors contributing to increased morbidity in shift workers is needed before the risks associated with these work schedules can be reduced. Simulated rotating shift work in mice, termed Environmental Circadian Disruption (ECD), leads to sleep loss, accelerates death, and dysregulates innate immune function. ECD-exposed mice exhibit pathologically severe inflammatory responses to bacterial endotoxin and increased infarct size following ischemic stroke. Our preliminary work has helped us establish a hypothesis that ECD disrupts the immune cell molecular circadian clock and produces a novel form of immunosuppression. We posit that this immunosuppression specifically slows anti-inflammatory signaling during an inflammatory challenge due to loss of adequate signaling through the TAM family of receptor tyrosine kinases, resulting in uncontrolled pro- inflammatory cytokine release and pathology. In this grant we will investigate the mechanistic underpinnings of the immunological consequences of ECD using newly developed in vitro ECD paradigms, laying the groundwork for translation of our work to human subjects exposed to laboratory-simulated and real-world shift work. The long term goal of this research effort is to develop screening tools and preventative medical treatments that may mitigate the adverse health consequences associated with work schedules that cause circadian disruption.
 描述(由申请人提供):轮班工人占美国工作人口的近20%,患多种癌症、肥胖症、糖尿病、中风和循环系统疾病的比例也相当高。更好地了解机械因素,有助于增加发病率在轮班工人之前,这些工作时间表的相关风险可以减少。在小鼠中模拟轮班工作,称为环境昼夜节律破坏(ECD),导致睡眠不足,加速死亡,先天免疫功能失调。暴露于ECD的小鼠表现出对细菌内毒素的病理性严重炎症反应和缺血性中风后梗死面积增加。我们的初步工作帮助我们建立了一个假设,即ECD破坏了免疫细胞的分子生物钟,并产生了一种新的免疫抑制形式。我们证实,由于通过受体酪氨酸激酶的TAM家族的足够信号传导的损失,这种免疫抑制在炎症激发期间特异性地减缓抗炎信号传导,导致不受控制的促炎细胞因子释放和病理学。在这项资助中,我们将使用新开发的体外ECD范式研究ECD免疫学后果的机制基础,为将我们的工作转化为暴露于实验室模拟和真实世界轮班工作的人类受试者奠定基础。这项研究工作的长期目标是开发筛查工具和预防性医学治疗,以减轻与导致昼夜节律紊乱的工作时间表相关的不良健康后果。

项目成果

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ALEC J DAVIDSON其他文献

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{{ truncateString('ALEC J DAVIDSON', 18)}}的其他基金

Visualizing hierarchical processing of photic input to the circadian clock in vivo
体内生物钟光输入的分层处理可视化
  • 批准号:
    10595100
  • 财政年份:
    2020
  • 资助金额:
    $ 35.38万
  • 项目类别:
Visualizing hierarchical processing of photic input to the circadian clock in vivo
体内生物钟光输入的分层处理可视化
  • 批准号:
    10374084
  • 财政年份:
    2020
  • 资助金额:
    $ 35.38万
  • 项目类别:
Visualizing hierarchical processing of photic input to the circadian clock in vivo
体内生物钟光输入的分层处理可视化
  • 批准号:
    10831723
  • 财政年份:
    2020
  • 资助金额:
    $ 35.38万
  • 项目类别:
Visualizing hierarchical processing of photic input to the circadian clock in vivo
体内生物钟光输入的分层处理可视化
  • 批准号:
    10160399
  • 财政年份:
    2020
  • 资助金额:
    $ 35.38万
  • 项目类别:
Visualizing the circadian neural network in vivo: A toolkit for real-time imaging and optogenetic manipulation of the suprachiasmatic nucleus
体内昼夜节律神经网络可视化:视交叉上核实时成像和光遗传学操作的工具包
  • 批准号:
    9586798
  • 财政年份:
    2018
  • 资助金额:
    $ 35.38万
  • 项目类别:
Novel mechanisms of immunological priming after circadian disruption
昼夜节律破坏后免疫启动的新机制
  • 批准号:
    8994291
  • 财政年份:
    2015
  • 资助金额:
    $ 35.38万
  • 项目类别:
MSM/WCI Partnership To Investigate Mechanisms Of Prostate Cancer (1 Of 2)
MSM/WCI 合作研究前列腺癌的机制(2 中的 1)
  • 批准号:
    7502650
  • 财政年份:
    2007
  • 资助金额:
    $ 35.38万
  • 项目类别:
MSM/WCI Partnership To Investigate Mechanisms Of Prostate Cancer (1 Of 2)
MSM/WCI 合作研究前列腺癌的机制(2 中的 1)
  • 批准号:
    7410225
  • 财政年份:
    2007
  • 资助金额:
    $ 35.38万
  • 项目类别:
Priority Setting Stage
优先级设定阶段
  • 批准号:
    7515891
  • 财政年份:
    2007
  • 资助金额:
    $ 35.38万
  • 项目类别:
Implementation Stage
实施阶段
  • 批准号:
    7515893
  • 财政年份:
    2007
  • 资助金额:
    $ 35.38万
  • 项目类别:

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开发作为抗炎剂和砷解毒剂的小分子抑制剂
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