IFN-Is at the interface of Innate and Adapative Immunity

IFN-Is 位于先天免疫和适应性免疫的界面

基本信息

项目摘要

DESCRIPTION (provided by applicant): Interferons (IFNs), first identified for their potent antiviral activity, can be divided into two major classes. Of these, type II or immune IFN (a.k.a. IFN-gamma) has earned much notoriety, but the type I IFNs (IFN-Is; e.g., IFN-alpha, IFN-beta, etc.) represent a much larger and complex family. Consistent with this, viruses have evolved numerous strategies to thwart IFN-I activity. More recently, IFN-Is have also achieved some celebrity with the recognition that they are the major effector cytokine secreted by plasmacvtoid dendritic cells (pDCs, a.k.a. "Natural IFN-I Producing Cells"). These IFN-Is then regulate aspects of both innate and adaptive immunity. There is also intriguing new evidence that IFN-Is and pDCs play an important role in the pathogenesis of Systemic Lupus Erythematosis (SLE). Like other cytokines, IFN-Is induce their potent activity through the induction of new genes. Characterization of the ability of IFN-alpha to rapidly induce genes led to the identification of Stat1 and Stat2, the first two STAT transcription factors. These STATs are recruited to the type I IFN receptor (IFNAR) by unknown mechanisms, whereupon they become activated (by tyrosine phosphorylation), dimerize, translocate to the nucleus and activate genes. In contrast, IFN-gamma transduces its signals solely through Stat1, albeit with differing kinetics. To determine the unique role Stat2 plays in the biological response to IFN-Is, Stat2 knockout mice were generated. These mice were highly susceptible to viral infection and partially unresponsive to IFN-Is. Unexpectedly, they exhibited tissue-specific differences in IFN-I stimulated Statl activation and a loss in the normal regulation of the Major Histocompatibility Complex class II (MHC-II). These observations highlight the important role type I IFNs play in regulating innate and adaptive immunity. To understand how IFN-Is mediate their many potent effects we propose to: 1. Determine how STATs are activated at the type I IFN receptor, including tissue specific differences. 2. Determine the unique role Stat2 exhibits in regulating MHC-II expression in macrophages 3. Explore the role SUMOylation may play in regulating the kinetics of IFN stimulated STATs.
描述(由申请人提供):干扰素(IFN),首先被鉴定为有效的抗病毒活性,可分为两大类。其中,II型或免疫IFN(a.k.a. IFN-γ)已经赢得了很多恶名,但是I型IFN(IFN-1;例如,IFN-α、IFN-β等)代表了一个更大更复杂的家庭与此一致,病毒已经进化出许多策略来阻碍IFN-1活性。最近,IFN-1也获得了一些知名度,认识到它们是由浆细胞样树突细胞(pDC,a.k.a.“天然IFN-I产生细胞”)。这些IFN-I然后调节先天免疫和适应性免疫两者的方面。还有有趣的新证据表明,IFN-1和pDC在系统性红斑狼疮(SLE)的发病机制中起重要作用。 与其他细胞因子一样,IFN-1通过诱导新基因来诱导其有效活性。IFN-α快速诱导基因的能力的表征导致了前两个STAT转录因子Stat 1和Stat 2的鉴定。这些STAT通过未知的机制被募集到I型IFN受体(IFNAR),于是它们被激活(通过酪氨酸磷酸化)、二聚化、易位到细胞核并激活基因。相反,IFN-γ仅通过Stat 1转导其信号,尽管动力学不同。 为了确定Stat 2在对IFN-1的生物学应答中发挥的独特作用,产生了Stat 2敲除小鼠。这些小鼠对病毒感染高度敏感,并且对IFN-1部分无反应。出乎意料的是,它们在IFN-1刺激的Stat 1活化和II类主要组织相容性复合物(MHC-II)的正常调节中表现出组织特异性差异。这些观察结果强调了I型IFN在调节先天性和适应性免疫中的重要作用。为了了解IFN-1是如何介导其许多有效作用的,我们建议: 1.确定STAT如何在I型IFN受体上被激活,包括组织特异性差异。 2.确定Stat 2在调节巨噬细胞MHC-II表达中的独特作用 3.探索SUMO化在调节IFN刺激的STAT的动力学中可能发挥的作用。

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 }}

CHRISTIAN W SCHINDLER其他文献

CHRISTIAN W SCHINDLER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('CHRISTIAN W SCHINDLER', 18)}}的其他基金

Genetic characterization of the murine type I Interferon locus
小鼠 I 型干扰素基因座的遗传特征
  • 批准号:
    8780594
  • 财政年份:
    2013
  • 资助金额:
    $ 30.42万
  • 项目类别:
Genetic characterization of the murine type I Interferon locus
小鼠 I 型干扰素基因座的遗传特征
  • 批准号:
    8623890
  • 财政年份:
    2013
  • 资助金额:
    $ 30.42万
  • 项目类别:
Probing the Innate Response to 3', 5'-cyclic Diguanylate (c-diGMP)
探索对 3, 5-环二鸟苷酸 (c-diGMP) 的先天反应
  • 批准号:
    8274633
  • 财政年份:
    2011
  • 资助金额:
    $ 30.42万
  • 项目类别:
Probing the Innate Response to 3', 5'-cyclic Diguanylate (c-diGMP)
探索对 3, 5-环二鸟苷酸 (c-diGMP) 的先天反应
  • 批准号:
    8176709
  • 财政年份:
    2011
  • 资助金额:
    $ 30.42万
  • 项目类别:
IFN-Is at the interface of Innate and Adapative Immunity
IFN-Is 位于先天免疫和适应性免疫的界面
  • 批准号:
    7916939
  • 财政年份:
    2009
  • 资助金额:
    $ 30.42万
  • 项目类别:
Characterization of the Innate Immune Response to Crystalline Silica
对结晶二氧化硅的先天免疫反应的表征
  • 批准号:
    7512740
  • 财政年份:
    2009
  • 资助金额:
    $ 30.42万
  • 项目类别:
Characterization of the Innate Immune Response to Crystalline Silica
对结晶二氧化硅的先天免疫反应的表征
  • 批准号:
    7846828
  • 财政年份:
    2009
  • 资助金额:
    $ 30.42万
  • 项目类别:
FLUORESCENCE-ACTIVATED CELL SORTER: DIABETES
荧光激活细胞分选仪:糖尿病
  • 批准号:
    6973150
  • 财政年份:
    2004
  • 资助金额:
    $ 30.42万
  • 项目类别:
FLUORESCENCE-ACTIVATED CELL SORTER: STEM CELLS: ADULT HUMAN, ADULT MOUSE
荧光激活细胞分选仪:干细胞:成年人类、成年小鼠
  • 批准号:
    6973147
  • 财政年份:
    2004
  • 资助金额:
    $ 30.42万
  • 项目类别:
FLUORESCENCE-ACTIVATED CELL SORTER: AIDS
荧光激活细胞分选仪:艾滋病
  • 批准号:
    6973148
  • 财政年份:
    2004
  • 资助金额:
    $ 30.42万
  • 项目类别:

相似海外基金

Tri-Signal Artificial Antigen Presenting Cells for Cancer Immunotherapy
用于癌症免疫治疗的三信号人工抗原呈递细胞
  • 批准号:
    10751133
  • 财政年份:
    2023
  • 资助金额:
    $ 30.42万
  • 项目类别:
Microfluidic Precision Engineered Artificial Antigen Presenting Cells for Cancer Immunotherapy
用于癌症免疫治疗的微流控精密工程人工抗原呈递细胞
  • 批准号:
    10696138
  • 财政年份:
    2022
  • 资助金额:
    $ 30.42万
  • 项目类别:
The role of microglia as antigen presenting cells in Globoid Cell Leukodystrophy
小胶质细胞作为抗原呈递细胞在球状细胞脑白质营养不良中的作用
  • 批准号:
    10663066
  • 财政年份:
    2022
  • 资助金额:
    $ 30.42万
  • 项目类别:
The role of microglia as antigen presenting cells in Globoid Cell Leukodystrophy
小胶质细胞作为抗原呈递细胞在球状细胞脑白质营养不良中的作用
  • 批准号:
    10537159
  • 财政年份:
    2022
  • 资助金额:
    $ 30.42万
  • 项目类别:
Analysis of the function of antigen-presenting cells present in the stroma of colorectal cancer and the intracellular microbiome
结直肠癌基质中抗原呈递细胞和细胞内微生物组的功能分析
  • 批准号:
    21K08723
  • 财政年份:
    2021
  • 资助金额:
    $ 30.42万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Class II artificial antigen presenting cells for cancer immunotherapy
用于癌症免疫治疗的 II 类人工抗原呈递细胞
  • 批准号:
    10156950
  • 财政年份:
    2021
  • 资助金额:
    $ 30.42万
  • 项目类别:
The role of CX3CR1+ antigen presenting cells in T cell selection and central tolerance"
CX3CR1抗原呈递细胞在T细胞选择和中枢耐受中的作用"
  • 批准号:
    10631854
  • 财政年份:
    2021
  • 资助金额:
    $ 30.42万
  • 项目类别:
Reprogramming Cancer Cells into Antigen Presenting Cells: Cancer Vaccination with mRNA Enabled by Charge-Altering Releasable Transporters
将癌细胞重编程为抗原呈递细胞:通过改变电荷的可释放转运蛋白实现 mRNA 的癌症疫苗接种
  • 批准号:
    10153927
  • 财政年份:
    2021
  • 资助金额:
    $ 30.42万
  • 项目类别:
Class II artificial antigen presenting cells for cancer immunotherapy
用于癌症免疫治疗的 II 类人工抗原呈递细胞
  • 批准号:
    10331830
  • 财政年份:
    2021
  • 资助金额:
    $ 30.42万
  • 项目类别:
Analysis on detrimental interplay between pathogenic helper T cells, inflammatory antigen-presenting cells and disease-associated microglia in chronic pathogenesis of multiple sclerosis
多发性硬化症慢性发病机制中致病性辅助 T 细胞、炎症抗原呈递细胞和疾病相关小胶质细胞之间的有害相互作用分析
  • 批准号:
    20K16294
  • 财政年份:
    2020
  • 资助金额:
    $ 30.42万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了