Adrenergic control of circadian rhythms in CD8 T cells responding to influenza
肾上腺素能控制响应流感的 CD8 T 细胞的昼夜节律
基本信息
- 批准号:10743822
- 负责人:
- 金额:$ 57.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:ADRB2 geneARNTL geneAccelerationAcuteAdrenergic AgentsAdrenergic ReceptorAreaArrhythmiaBindingBiological ClocksBiological ProcessCAR T cell therapyCD8-Positive T-LymphocytesCD8B1 geneCell physiologyCellsCircadian DysregulationCircadian RhythmsCircadian gene expressionCommunicable DiseasesCuesDarknessDevelopmentDiseaseEffector CellEpinephrineExhibitsFrequenciesGene ExpressionGenesGoalsHealthHumanImmuneImmune responseImmunityInfectionInflammationInflammatoryInfluenzaInfluenza A virusJet Lag SyndromeLightMammalsMeasuresMediatingModalityMolecularMusNatureNeuronsNeurotransmitter ReceptorNeurotransmittersNorepinephrineOutcomes ResearchPathway interactionsPeripheralPhasePhysiologyPlayPropertyPublishingPulmonary InflammationRoleSeverity of illnessSignal TransductionSympathetic Nervous SystemT cell responseT-Cell DevelopmentT-LymphocyteT-bet proteinTestingTherapeutic InterventionTimeTissuesVaccine DesignViral PathogenesisViral Respiratory Tract InfectionViral VaccinesVirusVirus DiseasesVirus Replicationadaptive immunityanti-cancerantiviral drug developmentbeta-2 Adrenergic Receptorscircadianeffector T cellhuman diseaseimprovedin vivoinfluenza infectioninterestlight entrainmentlung injurymouse modelpathogenpublic health relevancereceptorresponsetargeted treatmenttherapy designvirtual
项目摘要
PROJECT SUMMARY
This application seeks to understand how circadian rhythms control T cell immunity to influenza infection
through signals delivered by the sympathetic nervous system. Circadian rhythms are biological clocks that are
entrained by light/dark cycles, and in mammals, those rhythms are synchronized systemically throughout the
body via signals delivered by sympathetic and parasympathetic neurons. Our recent studies uncovered an
unexpected role for the β2-adrenergic receptor in cytolytic responses of CD8+ T cells to a virus infection.
Further, we found that selective deletion of the Adrb2 on CD8+ T cells profoundly disrupted circadian gene
expression and oscillation frequencies as a function of light/dark entrainment. This proposal will test the
hypothesis that the signaling through the ADRB2 in CD8+ T cells regulates circadian rhythm genes, and that
those genes are required for orchestrated T cell responses to influenza infection. Aim 1 will distinguish the roles
of the Adrb2 and downstream core clock in CD8-mediated lung inflammation during influenza infection. Aim 2
will determine how jet-lag impacts CD8+ T cell responses to influenza. This proposal tests a very straight-
forward hypothesis, which if supported, will be the first to connect a circadian rhythm entrainment receptor to
downstream T cells responses to influenza. The outcomes of this research will significantly advance our
understanding of environmental pathways that regulate immune responses to influenza and improve mouse
models of viral pathogenesis and vaccine design.
项目摘要
本申请旨在了解昼夜节律如何控制T细胞对流感感染的免疫力
通过交感神经系统传递的信号。昼夜节律是生物钟,
在哺乳动物中,这些节奏在整个过程中是系统同步的。
通过交感神经和副交感神经元传递的信号来控制身体。我们最近的研究发现,
β2-肾上腺素能受体在CD 8 + T细胞对病毒感染的细胞溶解反应中的意外作用。
此外,我们发现选择性缺失CD 8 + T细胞上的Adrb 2严重破坏了昼夜节律基因,
表达和振荡频率作为光/暗夹带的函数。这项提案将考验
假设通过CD 8 + T细胞中的ADRB 2的信号传导调节昼夜节律基因,
这些基因是协调T细胞对流感感染的反应所必需的。目标1将区分角色
Adrb 2和下游核心时钟在流感感染期间CD 8介导的肺部炎症中的作用。目的2
将决定时差如何影响CD 8 + T细胞对流感的反应。这是一个非常直接的测试-
这一假设如果得到支持,将是第一个将昼夜节律诱导受体与
下游T细胞对流感的反应。这项研究的成果将大大促进我们的
了解调节对流感的免疫反应并改善小鼠免疫功能的环境途径
病毒发病机理模型和疫苗设计。
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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John David FARRAR其他文献
John David FARRAR的其他文献
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{{ truncateString('John David FARRAR', 18)}}的其他基金
Type 1 Interferon-Regulated T Helper Development
1 型干扰素调节 T 辅助细胞的发育
- 批准号:
7847198 - 财政年份:2009
- 资助金额:
$ 57.78万 - 项目类别:
Type 1 Interferon-Regulated T Helper Development
1 型干扰素调节 T 辅助细胞的发育
- 批准号:
7342857 - 财政年份:2005
- 资助金额:
$ 57.78万 - 项目类别:
Type 1 Interferon-Regulated T Helper Development
1 型干扰素调节 T 辅助细胞的发育
- 批准号:
7577387 - 财政年份:2005
- 资助金额:
$ 57.78万 - 项目类别:
Type I Interferon-Regulated T Helper Development
I 型干扰素调节 T 辅助细胞的开发
- 批准号:
8703230 - 财政年份:2005
- 资助金额:
$ 57.78万 - 项目类别:
Type I Interferon-Regulated T Helper Development
I 型干扰素调节 T 辅助细胞的开发
- 批准号:
8416333 - 财政年份:2005
- 资助金额:
$ 57.78万 - 项目类别:
Type I Interferon-Regulated T Helper Development
I 型干扰素调节 T 辅助细胞的开发
- 批准号:
8211045 - 财政年份:2005
- 资助金额:
$ 57.78万 - 项目类别: