Macrophages as effectors of autoimmune valvular carditis

巨噬细胞作为自身免疫性瓣膜性心脏病的效应器

基本信息

  • 批准号:
    8890874
  • 负责人:
  • 金额:
    $ 36.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-07-15 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Our long-term goal is to understand how cardiovascular tissues are targeted for attack in the context of systemic autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this proposal we focus on macrophages, a key inflammatory cell type. Although the presence of macrophages in inflamed cardiovascular tissues in patients with these diseases has long been recognized, the tools to dissect their precise role in disease pathogenesis have only recently been developed. We propose to employ these powerful new tools to study how macrophages contribute to cardiovascular inflammation in the setting of systemic rheumatic diseases. We have recently described the occurrence of cardiac valve inflammation in a mouse model of autoimmune arthritis. Valvular carditis in this model is similar to that seen in rheumatic diseases in humans. The cytokine interleukin-17 (IL-17) and immune complexes interacting with activating Fc receptors are critical for carditis to develop. Importantly, macrophages are the predominant inflammatory cell type in this model. Macrophages are characterized broadly as M1 (classical/pro-inflammatory) or M2 (alternative/anti-inflammatory). Our preliminary data suggest that both of these populations may contribute to valvular carditis. We propose to study essential aspects of macrophage biology in this model system: entry into the cardiovascular tissue, activation, and effector function. First, we will determine how macrophages enter the cardiac valves, focusing on the cell surface receptor VLA-4. Next, we will explore how IL-17, activating Fc receptors and TLR4 drive macrophage activation toward M1 or M2 phenotypes. We will then dissect the relative contributions of the M1 and M2 macrophage populations to disease severity, by interfering with the differentiation of these cell subsets or with their key molecular products. Using recently-developed conditional gene knockout animals in conjunction with more traditional methods will allow us to interrogate the pathogenic mechanisms employed by macrophages in this system. Immune complexes, IL-17, and macrophage infiltration are hallmarks of many human autoimmune diseases. We propose to use our novel animal model system to begin to understand how these molecules and cells interact in vivo to provoke tissue pathology, with specific attention to the cardiac valves. The knowledge that we gain is expected to lead to new therapies to reduce the cardiovascular morbidity and mortality among patients with rheumatoid arthritis, lupus, and related autoimmune conditions.
描述(由申请人提供):我们的长期目标是了解在系统性自身免疫性疾病(如类风湿关节炎和系统性红斑狼疮)的背景下,心血管组织是如何被靶向攻击的。在这个建议中,我们关注巨噬细胞,一种关键的炎症细胞类型。虽然巨噬细胞在这些疾病患者的炎症心血管组织中的存在早已被认识到,但剖析其在疾病发病机制中的精确作用的工具直到最近才被开发出来。我们建议使用这些强大的新工具来研究巨噬细胞如何在系统性风湿性疾病的背景下促进心血管炎症。我们最近描述了自身免疫性关节炎小鼠模型中心脏瓣膜炎症的发生。该模型中的瓣膜性心炎与人类风湿性疾病中的瓣膜性心炎相似。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Bryce Binstadt其他文献

Bryce Binstadt的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Bryce Binstadt', 18)}}的其他基金

A novel autoinflammatory skin disease in a patient with mutations in alpha-T-catenin
α-T-连环蛋白突变患者的一种新型自身炎症性皮肤病
  • 批准号:
    10055124
  • 财政年份:
    2020
  • 资助金额:
    $ 36.6万
  • 项目类别:
A novel autoinflammatory skin disease in a patient with mutations in alpha-T-catenin
α-T-连环蛋白突变患者的一种新型自身炎症性皮肤病
  • 批准号:
    10197026
  • 财政年份:
    2020
  • 资助金额:
    $ 36.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    10624894
  • 财政年份:
    2014
  • 资助金额:
    $ 36.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    9815721
  • 财政年份:
    2014
  • 资助金额:
    $ 36.6万
  • 项目类别:
Macrophages as effectors of autoimmune valvular carditis
巨噬细胞作为自身免疫性瓣膜性心脏病的效应器
  • 批准号:
    9086419
  • 财政年份:
    2014
  • 资助金额:
    $ 36.6万
  • 项目类别:
Macrophages as effectors of autoimmune valvular carditis
巨噬细胞作为自身免疫性瓣膜性心脏病的效应器
  • 批准号:
    8754860
  • 财政年份:
    2014
  • 资助金额:
    $ 36.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    10418653
  • 财政年份:
    2014
  • 资助金额:
    $ 36.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    9926159
  • 财政年份:
    2014
  • 资助金额:
    $ 36.6万
  • 项目类别:
A mouse to track dual TCR T cells
追踪双 TCR T 细胞的小鼠
  • 批准号:
    8563789
  • 财政年份:
    2013
  • 资助金额:
    $ 36.6万
  • 项目类别:
A mouse to track dual TCR T cells
追踪双 TCR T 细胞的小鼠
  • 批准号:
    8660288
  • 财政年份:
    2013
  • 资助金额:
    $ 36.6万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 36.6万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了