Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways

IgE 介导的单核细胞抗病毒反应途径调节机制

基本信息

  • 批准号:
    10438876
  • 负责人:
  • 金额:
    $ 18.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-06-25 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract: Virus infections are highly associated with the exacerbation of allergic diseases including allergic asthma, atopic dermatitis, and allergic rhinitis. IgE-mediated allergic sensitization has been shown to impair antiviral responses by innate immune cells such as monocytes- enhancing pro-inflammatory cytokine secretion, disrupting phagocytosis, and inhibiting virus-induced maturation, IFN production, and altering CD4 T cell priming. These findings suggest a role for IgE-mediated signals in modulating innate antiviral signaling pathways, however little is known regarding the molecular mechanisms behind these observations. Given the significant morbidity and economic impact of allergic diseases, a thorough understanding of IgE-mediated effects on antiviral responses is critical for the discovery of new therapeutics for viral and allergic diseases. The goal of this study is to determine how IgE-mediated allergic stimulation inhibits monocyte antiviral responses to regulate cellular functions. Using primary human monocytes, we will utilize established molecular and biochemical techniques in combination with advanced flow cytometry techniques (flow cytometry imaging and mass cytometry) and transcriptomics to: (Aim 1) determine how IgE-mediated signaling components regulate early antiviral recognition pathways, (Aim 2) determine the mechanisms by which IgE-induced IL-10 regulates interferon receptor signaling, and (Aim 3) translate the in vitro findings by comparing monocyte antiviral responses in individuals with high and low serum IgE. These studies will fill a large gap in our current knowledge of how IgE-mediated processes modulate antiviral responses to promote virus-induced allergic exacerbations. Dr. Regina K. Rowe, M.D. Ph.D. is currently an Assistant Professor of Pediatric Infectious Diseases at the University of Rochester Medical Center. She received her Ph.D. from Washington University in St. Louis in Molecular Microbiology and Microbial Pathogenesis where she investigated the interactions of hantaviruses with the respiratory epithelium. She then received medical training at St. Louis University followed by Pediatric Residency and Infectious Disease Fellowship training at UT Southwestern where her postdoctoral research focused on the effects of allergic stimulation on monocyte-induced T cell priming. This career development award will expand her expertise in systems immunology through training in cell signaling mechanisms, advanced flow cytometry methods, and bioinformatics. As a pediatric physician-scientist, she will utilize her skills as an infectious disease specialist trained in both human immunology and virology to establish a scientific platform to answer a breadth of questions involving host-pathogen interactions in the context of human disease. Her innovative approaches have the potential to identify new therapeutics to treat virus-induced allergic diseases, and ultimately prevent disease development, exacerbation, and progression.
项目概要/摘要: 病毒感染与包括过敏性哮喘在内的过敏性疾病的恶化高度相关, 特应性皮炎和过敏性鼻炎。IgE介导的过敏性致敏已被证明损害抗病毒 先天免疫细胞如单核细胞的反应-增强促炎细胞因子分泌, 破坏吞噬作用,并抑制病毒诱导的成熟、IFN产生和改变CD 4 T细胞引发。 这些发现表明IgE介导的信号在调节先天性抗病毒信号通路中的作用, 然而,关于这些观察结果背后的分子机制知之甚少。鉴于重大的 过敏性疾病的发病率和经济影响,彻底了解IgE介导的影响, 抗病毒反应对于发现病毒和过敏性疾病的新疗法是至关重要的。这个目标 这项研究旨在确定IgE介导的过敏性刺激如何抑制单核细胞的抗病毒反应,以调节 细胞功能。使用原代人单核细胞,我们将利用已建立的分子和生物化学方法, 技术与先进的流式细胞术技术(流式细胞术成像和质量分析)相结合, 目的1)确定IgE介导的信号传导成分如何调节早期免疫应答, 抗病毒识别途径,(目的2)确定IgE诱导的IL-10调节 干扰素受体信号传导,并(目的3)通过比较单核细胞抗病毒药物 高和低血清IgE个体的反应。这些研究将填补我们目前知识的一个大空白 IgE介导的过程如何调节抗病毒反应以促进病毒诱导的过敏性加重。 Regina K.博士Rowe,医学博士博士目前是儿科传染病助理教授, 罗切斯特大学医学中心。她获得了博士学位。年,来自圣路易斯的华盛顿大学 分子微生物学和微生物发病机制,她研究了汉坦病毒与 呼吸道上皮然后,她在圣路易斯大学接受了医学培训, 在UT西南部的住院医师和传染病奖学金培训,她的博士后研究 集中于过敏性刺激对单核细胞诱导的T细胞引发的影响。这个职业发展奖 将通过细胞信号传导机制、高级流动和免疫学方面的培训, 细胞计数方法和生物信息学。作为一名儿科医生,科学家,她将利用她的技能, 在人类免疫学和病毒学方面接受培训的传染病专家建立了一个科学平台, 在人类疾病的背景下回答涉及宿主-病原体相互作用的广泛问题。她 创新的方法具有鉴定治疗病毒诱导的变应性疾病的新疗法的潜力, 并最终防止疾病发展、恶化和进展。

项目成果

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Regina Kay Rowe其他文献

Regina Kay Rowe的其他文献

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{{ truncateString('Regina Kay Rowe', 18)}}的其他基金

Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways
IgE介导的单核细胞抗病毒反应途径的调节机制
  • 批准号:
    10640247
  • 财政年份:
    2021
  • 资助金额:
    $ 18.53万
  • 项目类别:
Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways
IgE 介导的单核细胞抗病毒反应途径调节机制
  • 批准号:
    10282166
  • 财政年份:
    2021
  • 资助金额:
    $ 18.53万
  • 项目类别:

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