Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection
移行树突状细胞:确定病毒感染过程中新型先天免疫群体的起源和作用
基本信息
- 批准号:10350705
- 负责人:
- 金额:$ 56.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-12 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:Antigen PresentationAntigen-Presenting CellsAntigensAntiviral ResponseBiologicalBiological AssayCell Differentiation processCell physiologyCellsCharacteristicsDataDendritic CellsDependenceDevelopmentFutureGeneticGenetic TranscriptionGoalsHomologous GeneHumanImmuneImmune responseIn VitroInfectionInnate Immune ResponseInterferon Type IInterferonsLymphoidMaintenanceMediatingModelingMusMyelogenousNamesOutcomePathway interactionsPhenotypePlayPopulationProcessProductionProteomicsResearchResolutionRoleSiteSystemT cell factor 4T cell responseT-Cell ActivationT-Cell ProliferationT-LymphocyteTestingTherapeuticUnited StatesVirusVirus Diseasesadaptive immune responsebaseburden of illnesscell typedesignexperimental studyhigh dimensionalityimmune functionin vivoinnate immune functionmouse modelnovelnovel strategiesprogenitorrational designresponsesensortherapeutic developmenttranscription factortranscriptomicsvaccination strategy
项目摘要
ABSTRACT
Plasmacytoid dendritic cells (pDCs) are a unique subset of innate immune cells capable of multiple functions
essential for antiviral responses, including type I interferon production, antigen-presentation and T cell activation.
The mechanisms that govern these distinct pDC functions remain poorly defined; however, they could be
mediated by distinct subpopulations. Using high-dimensional single-cell proteomic and transcriptomic
approaches, we and others recently discovered a novel human dendritic cell (DC) population that is captured
within traditional pDC definitions. These cells harbor phenotypic features of both pDCs and conventional DC
subsets (cDCs); thus, we called them transitional DCs or tDCs. We have now performed an integrated
multidimensional comparison that resulted in the identification of the mouse homolog of human tDCs. The
discovery that tDCs occur in both human and mouse suggests they have an evolutionarily conserved role during
immune responses. However, tDC function has never been investigated. Similarly, the developmental origin of
tDCs has not yet been analyzed. This represents a fundamental gap in our understanding of the cellular
components that mediate innate immune responses against viruses and poses an impediment to the
development of therapeutics. Based on our preliminary data generated in mouse, we hypothesize that tDCs and
pDCs form a distinct developmental lineage that cooperates at the site of viral infection to modulate immune
responses. In three specific aims, we propose to query tDC origin, function and relationship with pDCs. To
achieve these aims, we will take advantage of high-dimensional approaches already established in our lab, in
vitro and in vivo differentiation assays, and novel lineage tracing and cell-specific depletion mouse models. We
anticipate that findings from this proposal will enhance our current understanding of innate cellular pathways that
result in the positive outcome of viral infection. Importantly, our integrated approach will incorporate analyses of
both mouse and human tDCs; thus, it has the potential to reveal features of the innate immune compartment
that are conserved between species. This proposal has the potential to impact the rational design of future
therapeutic strategies.
摘要
浆细胞样树突状细胞(Plasmacytoid dendritic cells,pDC)是一类具有多种免疫功能的天然免疫细胞
对于抗病毒反应至关重要,包括I型干扰素产生、抗原呈递和T细胞活化。
控制这些不同pDC功能的机制仍然不清楚;然而,它们可能是
由不同的亚群介导。使用高维单细胞蛋白质组学和转录组学
最近,我们和其他人发现了一种新的人类树突状细胞(DC)群体,
在传统的PDC定义中。这些细胞具有pDC和常规DC的表型特征
我们称之为过渡性DC或tDC。我们现在已经完成了一个综合的
多维比较,其导致人tDC的小鼠同源物的鉴定。的
tDC在人和小鼠中均存在的发现表明它们在人类发育过程中具有进化上保守的作用。
免疫反应。然而,tDC功能从未被研究过。同样,
tDC尚未被分析。这代表了我们对细胞的理解上的一个根本性的空白。
介导针对病毒的先天免疫反应并对免疫系统的免疫功能构成障碍的成分。
治疗学的发展。基于我们在小鼠中产生的初步数据,我们假设tDC和
pDC形成独特的发育谱系,其在病毒感染位点协同作用以调节免疫应答。
应答在三个具体目标中,我们提出了查询tDC的起源,功能和与pDC的关系。到
为了实现这些目标,我们将利用我们实验室已经建立的高维方法,
体外和体内分化测定,以及新的谱系追踪和细胞特异性耗竭小鼠模型。我们
预计这项提议的发现将增强我们目前对先天细胞通路的理解,
导致病毒感染的阳性结果。重要的是,我们的综合方法将纳入以下分析:
小鼠和人tDC;因此,它有潜力揭示先天免疫区室的特征,
在物种之间是保守的。这一建议有可能影响未来的合理设计,
治疗策略
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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Juliana Idoyaga其他文献
Juliana Idoyaga的其他文献
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{{ truncateString('Juliana Idoyaga', 18)}}的其他基金
Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection
移行树突状细胞:确定病毒感染过程中新型先天免疫群体的起源和作用
- 批准号:
10185957 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
From stomach tissue to cellular mechanisms: unraveling the role of mononuclear phagocytes in the pathophysiology of gastroparesis
从胃组织到细胞机制:揭示单核吞噬细胞在胃轻瘫病理生理学中的作用
- 批准号:
10493407 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection
移行树突状细胞:确定病毒感染过程中新型先天免疫群体的起源和作用
- 批准号:
10559630 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
Novel transcription factors modulating the development and function of pDCs and pDC-related cells
调节 pDC 和 pDC 相关细胞发育和功能的新型转录因子
- 批准号:
10414818 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
From stomach tissue to cellular mechanisms: unraveling the role of mononuclear phagocytes in the pathophysiology of gastroparesis
从胃组织到细胞机制:揭示单核吞噬细胞在胃轻瘫病理生理学中的作用
- 批准号:
10953591 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
Novel transcription factors modulating the development and function of pDCs and pDC-related cells
调节 pDC 和 pDC 相关细胞发育和功能的新型转录因子
- 批准号:
10288643 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
From stomach tissue to cellular mechanisms: unraveling the role of mononuclear phagocytes in the pathophysiology of gastroparesis
从胃组织到细胞机制:揭示单核吞噬细胞在胃轻瘫病理生理学中的作用
- 批准号:
10363328 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection
移行树突状细胞:确定病毒感染过程中新型先天免疫群体的起源和作用
- 批准号:
10911418 - 财政年份:2021
- 资助金额:
$ 56.06万 - 项目类别:
Effect of radiotherapy on dendritic cell subsets: implications for immunotherapy
放射治疗对树突状细胞亚群的影响:对免疫治疗的影响
- 批准号:
9566132 - 财政年份:2017
- 资助金额:
$ 56.06万 - 项目类别:
Effect of radiotherapy on dendritic cell subsets: implications for immunotherapy
放射治疗对树突状细胞亚群的影响:对免疫治疗的影响
- 批准号:
9752249 - 财政年份:2017
- 资助金额:
$ 56.06万 - 项目类别:
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