Role of SCARF1 in apoptotic cell clearance and prevention of autoimmunity

SCARF1 在凋亡细胞清除和预防自身免疫中的作用

基本信息

  • 批准号:
    9230810
  • 负责人:
  • 金额:
    $ 41.28万
  • 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:
    2015-09-01 至 2020-02-29
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Efficient detection and clearance of apoptotic cells is critical for control of tissue homeostasis. Professional phagocytes are responsible for removal of dying cells; however, defects in recognition or engulfment of apoptotic cells can lead to chronic inflammation and autoimmune disease. Accumulation of apoptotic cells in tissues has been associated with the autoimmune disease systemic lupus erythematosus (SLE), and several receptors on phagocytes responsible for apoptotic cell clearance have been identified. We recently discovered that the scavenger receptor SCARF1 plays an important role in sensing and engulfment of apoptotic cells. Dendritic cells use SCARF1 to capture apoptotic cells via C1q bound to exposed phosphatidylserine, a primary eat me signal that translocates from the inner to the outer leaflet of the cell membrane on dying cells. Scarf1 deficiency in mice leads to the accumulation of apoptotic cells in tissues and the spontaneous development of lupus-like autoimmune disease with the production of autoantibodies to chromatin, aberrant immune cell activation, dermatitis and nephritis. Our previous findings fill several major gaps in our understanding of apoptotic cell clearance and regulation of autoimmunity; however, additional work is needed to identify the mechanisms necessary for SCARF1-mediated removal of apoptotic cells and prevention of spontaneous autoimmunity in vivo. Because apoptotic cell clearance requires numerous receptors and bridging molecules in vivo, we hypothesize that the immune system has developed failsafe mechanisms involving multiple receptors and bridging proteins expressed by different cell types present in specific tissues for the removal of dying cells to maintain tolerance and prevent autoimmunity. To test these hypotheses we will, (1) determine the cell/tissue-specific role of Scarf1 deficiency in the spontaneous development of autoimmune disease; (2) determine the relative contribution of SCARF1, CD36 and C1q to apoptotic cell clearance and prevention of autoimmune disease; (3) define the domains in SCARF1 that mediate apoptotic cell recognition, phagocytosis, and signaling. Understanding the mechanisms by which discrete cell populations use SCARF1 to engulf apoptotic cells and prevent inflammation should enable the design of novel tailored drugs for autoimmune disorders by targeting SCARF1 in specific cell subsets.
 描述(由申请人提供):有效检测和清除凋亡细胞对于控制组织稳态至关重要。专职吞噬细胞负责清除垂死细胞;然而,识别或吞噬凋亡细胞的缺陷可导致慢性炎症和自身免疫性疾病。凋亡细胞在组织中的积累与自身免疫性疾病系统性红斑狼疮(SLE)有关,并且已经鉴定了吞噬细胞上负责凋亡细胞清除的几种受体。我们最近发现清道夫受体SCARF 1在凋亡细胞的感知和吞噬中起重要作用。树突状细胞使用SCARF 1通过与暴露的磷脂酰丝氨酸结合的C1 q捕获凋亡细胞,这是一种主要的进食信号,在垂死细胞上从细胞膜的内叶易位到外叶。小鼠Scarf 1缺陷导致组织中凋亡细胞的积累和狼疮样自身免疫性疾病的自发发展,产生针对染色质的自身抗体、异常免疫细胞活化、皮炎和肾炎。我们以前的研究结果填补了我们对凋亡细胞清除和自身免疫调节的理解中的几个主要空白;然而,需要更多的工作来确定SCARF 1介导的凋亡细胞清除和预防体内自发性自身免疫所需的机制。由于凋亡细胞的清除需要大量的受体和桥接分子在体内,我们假设,免疫系统已经开发出故障安全机制,涉及多种受体和桥接蛋白表达的不同类型的细胞存在于特定组织中的死亡细胞的去除,以保持耐受性和防止自身免疫。为了验证这些假设,我们将(1)确定Scarf 1缺陷在自身免疫性疾病自发发展中的细胞/组织特异性作用;(2)确定SCARF 1,CD 36和C1 q对凋亡细胞清除和预防自身免疫性疾病的相对贡献;(3)确定SCARF 1中介导凋亡细胞识别,吞噬作用和信号传导的结构域。了解离散细胞群使用SCARF 1吞噬凋亡细胞和预防炎症的机制,应该能够通过靶向特定细胞亚群中的SCARF 1来设计针对自身免疫性疾病的新型定制药物。

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 }}

JOSEPH EL EL-KHOURY其他文献

JOSEPH EL EL-KHOURY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('JOSEPH EL EL-KHOURY', 18)}}的其他基金

Deciphering the role of Microglia in Glioblastoma
破译小胶质细胞在胶质母细胞瘤中的作用
  • 批准号:
    10584233
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
Deciphering the role of Microglia in Glioblastoma
破译小胶质细胞在胶质母细胞瘤中的作用
  • 批准号:
    10708972
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
Deciphering the role of Microglia in Glioblastoma
破译小胶质细胞在胶质母细胞瘤中的作用
  • 批准号:
    10416151
  • 财政年份:
    2021
  • 资助金额:
    $ 41.28万
  • 项目类别:
Role of SCARF1 in apoptotic cell clearance and prevention of autoimmunity
SCARF1 在凋亡细胞清除和预防自身免疫中的作用
  • 批准号:
    9424643
  • 财政年份:
    2015
  • 资助金额:
    $ 41.28万
  • 项目类别:
Toll-Like Receptor Signaling in Alzheimer's Disease
阿尔茨海默病中的 Toll 样受体信号转导
  • 批准号:
    8679097
  • 财政年份:
    2013
  • 资助金额:
    $ 41.28万
  • 项目类别:
Generation of a comprehensive panel of reagents for research on scavenger recepto
生成用于清除剂受体研究的综合试剂组
  • 批准号:
    8058800
  • 财政年份:
    2009
  • 资助金额:
    $ 41.28万
  • 项目类别:
Generation of a comprehensive panel of reagents for research on scavenger recepto
生成用于清除剂受体研究的综合试剂组
  • 批准号:
    7787085
  • 财政年份:
    2009
  • 资助金额:
    $ 41.28万
  • 项目类别:
Generation of a comprehensive panel of reagents for research on scavenger recepto
生成用于清除剂受体研究的综合试剂组
  • 批准号:
    7928276
  • 财政年份:
    2009
  • 资助金额:
    $ 41.28万
  • 项目类别:
Generation of a comprehensive panel of reagents for research on scavenger recepto
生成用于清除剂受体研究的综合试剂组
  • 批准号:
    7883973
  • 财政年份:
    2009
  • 资助金额:
    $ 41.28万
  • 项目类别:
Generation of a comprehensive panel of reagents for research on scavenger recepto
生成用于清除剂受体研究的综合试剂组
  • 批准号:
    7664665
  • 财政年份:
    2009
  • 资助金额:
    $ 41.28万
  • 项目类别:

相似海外基金

Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases
细胞中激活凋亡半胱天冬酶的生/死决策的机制
  • 批准号:
    10607815
  • 财政年份:
    2023
  • 资助金额:
    $ 41.28万
  • 项目类别:
Nuclear and chromatin aberrations during non-apoptotic cell death in C. elegans and mammals
线虫和哺乳动物非凋亡细胞死亡过程中的核和染色质畸变
  • 批准号:
    10723868
  • 财政年份:
    2023
  • 资助金额:
    $ 41.28万
  • 项目类别:
Non-apoptotic functions of caspase-3 in neural development
Caspase-3在神经发育中的非凋亡功能
  • 批准号:
    10862033
  • 财政年份:
    2023
  • 资助金额:
    $ 41.28万
  • 项目类别:
Apoptotic Donor Leukocytes to Promote Kidney Transplant Tolerance
凋亡供体白细胞促进肾移植耐受
  • 批准号:
    10622209
  • 财政年份:
    2023
  • 资助金额:
    $ 41.28万
  • 项目类别:
Design of apoptotic cell mimetic anti-inflammatory polymers for the treatment of cytokine storm
用于治疗细胞因子风暴的模拟凋亡细胞抗炎聚合物的设计
  • 批准号:
    22H03963
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Identifying the mechanisms behind non-apoptotic functions of mitochondrial matrix-localized MCL-1
确定线粒体基质定位的 MCL-1 非凋亡功能背后的机制
  • 批准号:
    10537709
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
Environmental Carcinogens Induce Minority MOMP to Initiate Carcinogenesis in Lung Cancer and Mesothelioma whileMaintaining Apoptotic Resistance via Mcl-1
环境致癌物诱导少数 MOMP 引发肺癌和间皮瘤的癌变,同时通过 Mcl-1 维持细胞凋亡抵抗
  • 批准号:
    10356565
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
  • 批准号:
    10708827
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
Activation of non-apoptotic cell death by the DNA damage response
DNA 损伤反应激活非凋亡细胞死亡
  • 批准号:
    10388929
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
Role of natural immunity to self apoptotic exosomes in maintaining immune homeostasis
对自凋亡外泌体的自然免疫在维持免疫稳态中的作用
  • 批准号:
    RGPIN-2021-03004
  • 财政年份:
    2022
  • 资助金额:
    $ 41.28万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了