Effect of Th2-type microenvironment on CD8 TRM-mediated protection from infection
Th2型微环境对CD8 TRM介导的感染保护作用的影响
基本信息
- 批准号:10624943
- 负责人:
- 金额:$ 57.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-19 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAdultAllergic DiseaseAnti-Bacterial AgentsAtopic DermatitisBacterial GenesBiological MarkersCD8-Positive T-LymphocytesCD8B1 geneCellsChromatinCutaneousDataDiseaseEczemaEczema HerpeticumEczema VaccinatumEnvironmentExposure toExtrinsic asthmaFocal InfectionGene ExpressionGenesGoalsHerpes Simplex InfectionsHumanImmune responseImpairmentIndividualInfectionInfectious Skin DiseasesInflammationInflammatoryIntegrinsInterleukin-13Interleukin-4IntestinesInvadedLeukocytesLungMaintenanceMalignant NeoplasmsMeasuresMediatingMemoryMorbidity - disease rateMusNuclear TranslocationPatientsPeripheralPhenotypePhosphorylationPredispositionProliferatingPsoriasisRecurrenceRiskRoleSamplingSignal TransductionSimplexvirusSkinTestingTissuesTransforming Growth Factor betaVaccinia virusViralVirus DiseasesVirus ReplicationWild Type Mouseantigen challengecytokinecytotoxiceffector T cellimmune functionimprovedin vivoinhibitormortalitymouse modelneutralizing antibodynovel therapeuticspathogenpreventprotein expressionreceptorrecruitresponsetranscription factortreatment effecttumor
项目摘要
Project Summary Abstract
Individuals suffering from atopic dermatitis have increased risk for serious recurrent and disseminated viral
infections, but the cause is unclear. Defense against local infections relies on tissue resident memory CD8+ T
cells (TRM) that deliver rapid defense against invading pathogens. We hypothesize that impairment of CD8+ TRM
contributes to severe infection in patients with atopic dermatitis. Our preliminary data demonstrate that IL-4
counters TGF-b-induced expression of CD8+ TRM receptors that are required for persistence within peripheral
tissues. In parallel, in vivo studies reveal that exposure of CD8+ T cells to IL-4 decreases their accumulation
within inflamed skin. Based on these preliminary data, we hypothesize that IL-4 prevents TGF-b-mediated
signaling and/or changes the chromatin landscape surrounding TGF-b target genes in CD8+ T cells, resulting
in an altered CD8+ T cell phenotype. We predict that these phenotypic changes impede the long-term
persistence of cutaneous CD8+ TRM and impair TRM-mediated defense against local viral infection. We will test
these hypotheses by i) using mouse models of allergic eczema to analyze the impact of local Th2-type
inflammation on CD8+ TRM persistence and protection from HSV infection ii) analyzing the effect of Th2
cytokines on the phenotype and function of human CD8+ TRM, and iii) investigating the impact of IL-4 on TGF-
bR signaling and the chromatin landscape of CD8+ T cells.
项目摘要
患有特应性皮炎的个体具有增加的严重复发性和传播性病毒感染的风险。
感染,但原因尚不清楚。防御局部感染依赖于组织驻留记忆CD 8 + T
细胞(TRM),提供快速防御入侵的病原体。我们假设CD 8 + TRM的损伤
导致特应性皮炎患者严重感染。我们的初步数据表明,IL-4
对抗TGF-β诱导的CD 8 + TRM受体表达,这是外周血中持续存在所必需的。
组织中与此同时,体内研究表明,CD 8 + T细胞暴露于IL-4会降低其积累
在发炎的皮肤里基于这些初步的数据,我们假设IL-4可以阻止TGF-β介导的
信号传导和/或改变CD 8 + T细胞中TGF-β靶基因周围的染色质景观,
改变的CD 8 + T细胞表型。我们预测这些表型变化会阻碍长期的
皮肤CD 8 + TRM的持续存在和TRM介导的对局部病毒感染的防御受损。我们将测试
i)使用过敏性湿疹的小鼠模型来分析局部Th 2-型的影响,
炎症对CD 8 + TRM持续性和对HSV感染的保护作用ii)分析Th 2
iii)研究IL-4对TGF-β 1表达的影响,
bR信号传导和CD 8 + T细胞的染色质景观。
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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SHANNON K BROMLEY其他文献
SHANNON K BROMLEY的其他文献
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{{ truncateString('SHANNON K BROMLEY', 18)}}的其他基金
Effect of allergic asthma on CD8+ TRM-mediated protection from infection
过敏性哮喘对 CD8 TRM 介导的感染保护作用的影响
- 批准号:
10495217 - 财政年份:2021
- 资助金额:
$ 57.93万 - 项目类别:
Effect of allergic asthma on CD8+ TRM-mediated protection from infection
过敏性哮喘对 CD8 TRM 介导的感染保护作用的影响
- 批准号:
10353929 - 财政年份:2021
- 资助金额:
$ 57.93万 - 项目类别:
Mechanisms of CD49a Expression and Resident Memory T Cell Formation in Skin.
皮肤中 CD49a 表达和常驻记忆 T 细胞形成的机制。
- 批准号:
9302659 - 财政年份:2016
- 资助金额:
$ 57.93万 - 项目类别:
Balance of chemokine entry and exit signals controls T cell accumulation in skin
趋化因子进入和退出信号的平衡控制皮肤中 T 细胞的积累
- 批准号:
7222766 - 财政年份:2006
- 资助金额:
$ 57.93万 - 项目类别:
Balance of chemokine entry and exit signals controls T cell accumulation in skin
趋化因子进入和退出信号的平衡控制皮肤中 T 细胞的积累
- 批准号:
7590369 - 财政年份:2006
- 资助金额:
$ 57.93万 - 项目类别:
Balance of chemokine entry and exit signals controls T cell accumulation in skin
趋化因子进入和退出信号的平衡控制皮肤中 T 细胞的积累
- 批准号:
7393238 - 财政年份:2006
- 资助金额:
$ 57.93万 - 项目类别:
Balance of chemokine entry and exit signals controls T cell accumulation in skin
趋化因子进入和退出信号的平衡控制皮肤中 T 细胞的积累
- 批准号:
7789488 - 财政年份:2006
- 资助金额:
$ 57.93万 - 项目类别:
Balance of chemokine entry and exit signals controls T cell accumulation in skin
趋化因子进入和退出信号的平衡控制皮肤中 T 细胞的积累
- 批准号:
7085722 - 财政年份:2006
- 资助金额:
$ 57.93万 - 项目类别:
CCR7 and CCR9 in T Cell Development and Trafficking
T 细胞发育和运输中的 CCR7 和 CCR9
- 批准号:
6695301 - 财政年份:2003
- 资助金额:
$ 57.93万 - 项目类别:
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