Innate cytokine responses that regulate autoimmunity

调节自身免疫的先天细胞因子反应

基本信息

  • 批准号:
    8212189
  • 负责人:
  • 金额:
    $ 35.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-04-01 至 2013-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Progress in the research funded by this grant has led to the discovery that the Osteopontin gene specifies two distinct isoforms through differential translation of a single Opn RNA species: a cytokine in T cells and a critical intracellular protein expressed in dendritic cells. We have shown that Opn expression in plasmacytoid dendritic cells is essential for production of this cell's signature cytokine- interferon alpha. We have recently discovered that robust Th17 responses depend on the ability of a newly-defined intracellular Opn isoform- Opn-i - to inhibit secretion of IL-27 by DC. We have also defined an Opn-i-dependent interaction that prevents efficient development of Th17 responses. Interferon alpha/beta receptor (IFNAR)-dependent inhibition of Opn-i expression releases the brakes on IL-27 secretion and inhibits the Th17 response to self-peptides. Definition of the impact of this IFNAR:Opn-i axis on the Th1 and Th17 response has provided new insight into the basis for the therapeutic effects of IFN-I in Multiple Sclerosis and other Th17 diseases, as well as a rationale for new therapeutic approaches that engage this IFNAR:Opn-i pathway. We propose experiments (1) to define the genetic mechanism resulting in generation of Opn-i and Opn-s expression in DC and T cells; (2) to define the interaction between Opn-i and the MyD88 signaling module in plasmacytoid DC leading to IFN1 expression and enhanced Th1 development; (3) to analyze Opn-dependent interactions in conventional DC that regulate antigen presentation and Th17 development and (4) to generate mice that selectively express distinct Opn isoforms so that we may determine the contribution of Opn isoforms to the immune response to foreign and self antigens in the context of Experimental Autoimmune Encephalomyelitis (EAE mu model of MS. PUBLIC HEALTH RELEVANCE: The Osteopontin (Opn) gene is important in diverse biological processes, including immune responses, vascularization and bone formation, through its interaction with different cell types. Our recent discovery of the contribution of distinct secreted and intracellular isoforms of Opn to the generation of Th17 and Th1 subsets fills an important gap in understanding the genesis of these subsets in normal and autoimmune responses. We will generate mutant mice that express the intracellular or secreted Opn isoform for analysis of the contribution of each to protection again infection and in a murine model of Multiple Sclerosis.
描述(由申请人提供):该基金资助的研究进展导致发现骨桥蛋白基因通过单个Opn RNA种类的差异翻译指定两种不同的同种型:T细胞中的细胞因子和树突状细胞中表达的关键细胞内蛋白。我们已经表明,Opn在浆细胞样树突状细胞中的表达对于产生这种细胞的标志性细胞因子-干扰素α是必不可少的。我们最近发现,强大的Th 17应答依赖于新定义的细胞内Opn同种型- Opn-i -抑制DC分泌IL-27的能力。我们还定义了Opn-i依赖性相互作用,其阻止Th 17应答的有效发展。Opn-i表达的干扰素α/β受体(IFNAR)依赖性抑制释放了对IL-27分泌的制动,并抑制了Th 17对自身肽的应答。这种IFNAR:Opn-i轴对Th 1和Th 17应答的影响的定义为IFN-I在多发性硬化症和其他Th 17疾病中的治疗作用的基础提供了新的见解,以及参与这种IFNAR:Opn-i途径的新治疗方法的原理。我们提出实验(1)确定导致DC和T细胞中Opn-i和Opn-s表达产生的遗传机制;(2)确定Opn-i和MyD 88信号传导模块在浆细胞样DC中导致IFN 1表达和增强的Th 1发育之间的相互作用;(3)分析常规DC中调节抗原呈递和Th 17发育的Opn依赖性相互作用,以及(4)产生选择性表达不同Opn同种型的小鼠,以便我们可以确定Opn同种型在实验性自身免疫性脑脊髓炎背景下对外来和自身抗原的免疫应答中的贡献。(EAE mu模型MS.公共卫生相关性:骨桥蛋白(Opn)基因通过与不同细胞类型的相互作用在多种生物过程中非常重要,包括免疫反应、血管形成和骨形成。我们最近发现的贡献不同的分泌型和细胞内亚型的Opn的Th 17和Th 1亚群的产生填补了一个重要的空白,了解这些亚群在正常和自身免疫反应的起源。我们将产生表达细胞内或分泌的Opn同种型的突变小鼠,用于分析每种同种型对再次感染和多发性硬化的鼠模型中的保护作用。

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 }}

HARVEY CANTOR其他文献

HARVEY CANTOR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('HARVEY CANTOR', 18)}}的其他基金

Immunologic mechanisms that prevent autoimmunity
预防自身免疫的免疫机制
  • 批准号:
    10265652
  • 财政年份:
    2020
  • 资助金额:
    $ 35.65万
  • 项目类别:
THE T-CELL RESPONSE TO ANTIGEN
T 细胞对抗原的反应
  • 批准号:
    6374616
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
Regulation of the follicular T-cell response to autoimmunity
滤泡 T 细胞对自身免疫反应的调节
  • 批准号:
    10066305
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
THE T-CELL RESPONSE TO ANTIGEN
T 细胞对抗原的反应
  • 批准号:
    6511531
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
Innate cytokine responses that regulate autoimmunity
调节自身免疫的先天细胞因子反应
  • 批准号:
    7650695
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
THE T-CELL RESPONSE TO ANTIGEN
T 细胞对抗原的反应
  • 批准号:
    6632442
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
THE T-CELL RESPONSE TO ANTIGEN
T 细胞对抗原的反应
  • 批准号:
    6196857
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
Regulation of the follicular T-cell response to autoimmunity
滤泡 T 细胞对自身免疫反应的调节
  • 批准号:
    9199455
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
Innate cytokine responses that regulate autoimmunity
调节自身免疫的先天细胞因子反应
  • 批准号:
    7768461
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:
THE T-CELL RESPONSE TO ANTIGEN
T 细胞对抗原的反应
  • 批准号:
    6721340
  • 财政年份:
    2000
  • 资助金额:
    $ 35.65万
  • 项目类别:

相似海外基金

Defining MHC class I restricted antigen presentation to CD8 T cells in experimental AD and Tauopathy - Supplement
定义实验性 AD 和 Tau 病中 MHC I 类限制性抗原呈递至 CD8 T 细胞 - 补充
  • 批准号:
    10836880
  • 财政年份:
    2023
  • 资助金额:
    $ 35.65万
  • 项目类别:
Targeting MAL2-mediated endocytosis to enhance tumor cell antigen presentation
靶向 MAL2 介导的内吞作用以增强肿瘤细胞抗原呈递
  • 批准号:
    10734324
  • 财政年份:
    2023
  • 资助金额:
    $ 35.65万
  • 项目类别:
Antigen presentation to the adaptive immune system in the choroid contributes to ocular autoimmune disease
脉络膜中的适应性免疫系统的抗原呈递导致眼部自身免疫性疾病
  • 批准号:
    10740465
  • 财政年份:
    2023
  • 资助金额:
    $ 35.65万
  • 项目类别:
Investigation of Target Protein Degradation and Its Effect on Enhancing Cancer-Specific Antigen Presentation by Quantitative Mass Spectrometry
通过定量质谱研究靶蛋白降解及其对增强癌症特异性抗原呈递的影响
  • 批准号:
    23K04971
  • 财政年份:
    2023
  • 资助金额:
    $ 35.65万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Promoting cancer cells' antigen presentation for serving as better targets for T cell immunotherapy
促进癌细胞的抗原呈递,作为 T 细胞免疫治疗的更好靶点
  • 批准号:
    2885451
  • 财政年份:
    2023
  • 资助金额:
    $ 35.65万
  • 项目类别:
    Studentship
Targeting immunoproteasome-mediated antigen presentation in colorectal cancer immunotherapy
结直肠癌免疫治疗中靶向免疫蛋白酶体介导的抗原呈递
  • 批准号:
    10385926
  • 财政年份:
    2022
  • 资助金额:
    $ 35.65万
  • 项目类别:
Lipid Antigen Presentation as a Driver of T2D Inflammation
脂质抗原呈递作为 T2D 炎症的驱动因素
  • 批准号:
    10509043
  • 财政年份:
    2022
  • 资助金额:
    $ 35.65万
  • 项目类别:
Enhancing antigen presentation in triple negative breast cancers through CD40 agonist, Flt3 ligand, and anthracycline chemotherapy
通过 CD40 激动剂、Flt3 配体和蒽环类化疗增强三阴性乳腺癌的抗原呈递
  • 批准号:
    10704008
  • 财政年份:
    2022
  • 资助金额:
    $ 35.65万
  • 项目类别:
Sex Differences in lipid antigen presentation, impact of lipid antigen presentation on peripheral lipid metabolism
脂质抗原呈递的性别差异,脂质抗原呈递对外周脂质代谢的影响
  • 批准号:
    10818273
  • 财政年份:
    2022
  • 资助金额:
    $ 35.65万
  • 项目类别:
Enhancing antigen presentation in triple negative breast cancers through CD40 agonist, Flt3 ligand, and anthracycline chemotherapy
通过 CD40 激动剂、Flt3 配体和蒽环类化疗增强三阴性乳腺癌的抗原呈递
  • 批准号:
    10349397
  • 财政年份:
    2022
  • 资助金额:
    $ 35.65万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了