Development of Immune Tolerance
免疫耐受的发展
基本信息
- 批准号:10338131
- 负责人:
- 金额:$ 46.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-03-15 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectAntigensAutoantigensAutoimmune DiseasesAutoimmunityBacteriaBiologyCellsComplexCoronavirusDataDendritic CellsDevelopmentDiseaseFOXP3 geneFundingGene ExpressionGenesGrantHybridomasIL2RA geneImiquimodImmuneImmune ToleranceImmune responseInfectious AgentInflammationInfluenzaInterferon Type IInterferon-betaInterferonsLoxP-flanked alleleLupusMediatingModelingMusOrganismPathogenicityPathologyPeptidesPlayPreventionProcessRegulatory T-LymphocyteRoleSTAT1 geneSignal TransductionSjogren&aposs SyndromeSourceSpecificityStromal CellsStructure of parenchyma of lungSystemic Lupus ErythematosusT-Cell Receptor GenesT-LymphocyteTestingThymic epithelial cellThymus GlandTissuesUp-RegulationViralVirusVirus Diseasescell typegenetic signaturein vivoinfluenza infectionmigrationmouse modelnovelpandemic influenzapathogenpreventprogenitorprogramsreduce symptomsresponsesecondary lymphoid organsingle-cell RNA sequencingtranscriptomics
项目摘要
PROJECT SUMMARY
Programming of self-antigen specific CD4+ Tregs in the thymus is essential for suppression of aberrant
immune responses and prevention of autoimmunity. Tregs also control inflammation during viral infection and
following pathogen clearance. This is particularly relevant for some types of viral infections such as the 1918
influenza pandemic strain, and more recently, specific strains of coronaviruses, where the immune response
itself can be pathogenic. In addition to viral infections, high levels of type I IFN are a defining feature of some
autoimmune diseases, such as SLE or Sjögren’s syndrome; Tregs reduce the symptoms of such autoimmune
diseases as well. However, we know relatively little about the Tregs involved in either of the above processes.
For example, what types of Tregs are involved in these responses? Do Tregs that dampen anti-viral immune
responses or suppress SLE-like disease develop in the thymus? If so, what is the thymic niche that controls
differentiation of this Treg subset? What APCs/stromal cells are required for differentiation of this Treg subset?
What specific functional roles does this Treg subset play during viral infections or SLE? Our preliminary data
demonstrate that a unique subset of Tregs develops in the thymus characterized by a strong
interferon-stimulated gene-signature (ISG-Tregs). We propose that this ISG-Treg subset plays a key
role in governing antiviral immune responses and suppressing immune responses to autoimmune
diseases characterized by high levels of IFN. We will explore this hypothesis in two specific aims. In aim 1,
we will determine how IFN signaling in the thymus affects thymic selection and the development of ISG-Tregs.
In aim 2, we will determine the functions of ISG-Tregs in response to viral infections and systemic lupus
erythematosis. Successful completion of these aims will allow us to identify the mechanism by which ISG-
Tregs arise in the thymus, and determine the role of ISG-Tregs in immune responses to viruses, and in
autoimmune diseases associated with high levels of IFN, such as SLE or Sjögren’s syndrome.
项目摘要
胸腺中自身抗原特异性CD 4 + T细胞的程序化对于抑制异常免疫应答是必需的。
免疫应答和自身免疫的预防。在病毒感染期间,Tactinase还控制炎症,
病原体清除后。这对于某些类型的病毒感染特别相关,例如1918年的
流感大流行毒株,以及最近的冠状病毒的特定毒株,其中免疫反应
本身就可能是致病的。除了病毒感染外,高水平的I型IFN是某些肿瘤的定义特征。
自身免疫性疾病,如SLE或舍格伦综合征; TdR减少这种自身免疫性疾病的症状
疾病也是。然而,我们对上述两个过程中涉及的TdR知之甚少。
例如,在这些反应中涉及哪些类型的T细胞?抑制抗病毒免疫力的激素
反应或抑制SLE样疾病在胸腺中的发展?如果是的话,控制着
这个Treg亚群的分化?这种Treg亚群的分化需要哪些APC/基质细胞?
这个Treg亚群在病毒感染或SLE期间发挥什么特定的功能作用?我们的初步数据
证明了一个独特的亚群TcR在胸腺中发育,其特征是强烈的
干扰素刺激的基因签名(ISG-THEB)。我们认为,ISG-Treg亚群在免疫调节中起着关键作用。
在控制抗病毒免疫应答和抑制自身免疫应答中的作用
以高水平IFN为特征的疾病。我们将在两个具体目标中探讨这一假设。在目标1中,
我们将确定胸腺中的IFN信号传导如何影响胸腺选择和ISG-T细胞的发育。
在目标2中,我们将确定ISG-TdR在病毒感染和系统性狼疮中的功能
尿道炎成功完成这些目标将使我们能够确定ISG-
T细胞在胸腺中产生,并决定ISG-T细胞在对病毒的免疫应答中的作用,
与高水平IFN相关的自身免疫性疾病,如SLE或干燥综合征。
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)
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Michael Archibald Farrar其他文献
Michael Archibald Farrar的其他文献
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{{ truncateString('Michael Archibald Farrar', 18)}}的其他基金
Regulation of central tolerance and Treg development by recirculating Treg
通过再循环 Treg 调节中枢耐受和 Treg 发育
- 批准号:
10615598 - 财政年份:2022
- 资助金额:
$ 46.01万 - 项目类别:
Regulation of central tolerance and Treg development by recirculating Treg
通过再循环 Treg 调节中枢耐受和 Treg 发育
- 批准号:
10363236 - 财政年份:2022
- 资助金额:
$ 46.01万 - 项目类别:
Co-repressors in STAT5-dependent CD4+ T Cell Development and Function
STAT5 依赖性 CD4 T 细胞发育和功能中的共阻遏物
- 批准号:
10614429 - 财政年份:2019
- 资助金额:
$ 46.01万 - 项目类别:
Pre-BCR and STAT5 Signaling in Acute Lymphoblastic Leukemia
急性淋巴细胞白血病中的前 BCR 和 STAT5 信号转导
- 批准号:
10059179 - 财政年份:2019
- 资助金额:
$ 46.01万 - 项目类别:
Pre-BCR and STAT5 Signaling in Acute Lymphoblastic Leukemia
急性淋巴细胞白血病中的前 BCR 和 STAT5 信号转导
- 批准号:
10319979 - 财政年份:2019
- 资助金额:
$ 46.01万 - 项目类别:
Pre-BCR and STAT5 Signaling in Acute Lymphoblastic Leukemia
急性淋巴细胞白血病中的前 BCR 和 STAT5 信号转导
- 批准号:
10550155 - 财政年份:2019
- 资助金额:
$ 46.01万 - 项目类别:
Co-repressors in STAT5-dependent CD4+ T Cell Development and Function
STAT5 依赖性 CD4 T 细胞发育和功能中的共阻遏物
- 批准号:
10382260 - 财政年份:2019
- 资助金额:
$ 46.01万 - 项目类别:
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