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。
基本信息
- 批准号:9302659
- 负责人:
- 金额:$ 41.69万
- 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:2016-06-23 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdhesionsAdhesivesAffectAllergic DiseaseAnti-Bacterial AgentsAntigensAtopic DermatitisAutoimmune DiseasesAutoimmune ProcessAutoimmune ResponsesBacterial GenesBasement membraneBiologyCD8-Positive T-LymphocytesCD8B1 geneCellsCollagenCollagen ReceptorsCutaneousDataDermisDevelopmentDiseaseE-CadherinEnvironmentEpidermisEpithelial CellsExtracellular MatrixFocal InfectionGoalsHealthHerpesvirus 1Host DefenseHumanImmuneImmune TargetingImmune responseImmune systemIn SituIndividualInfectionInfectious AgentInflammationInflammatoryIntegrinsInterleukin-4LinkMaintenanceMediatingMemoryModelingMolecularMorphologyMusOrganPathway interactionsPeripheralPlayPopulationPredispositionRecruitment ActivityRecurrenceRegulationSignal TransductionSimplexvirusSiteSkinT memory cellT-LymphocyteTestingTherapeuticTherapeutic UsesTissuesTransforming Growth Factor betaVaccine DesignVaccinesViralVitiligoadhesion receptorantigen challengeautoreactivitybasecell motilityclinical applicationcytokineintegrin alpha1beta1interstitialinterstitial cellmelanocytemigrationmouse modelnovelnovel therapeuticspathogenpreventreceptorreceptor expressionresponseskin disordertargeted treatment
项目摘要
The immune system must defend the host at the most likely sites of pathogen encounter--the epithelial cell
boundaries between barrier organs and the host's environment. Exciting recent data demonstrate that a
population of memory T cells (TRM) resides long-term within peripheral tissues and provides a first line of host
defense from pathogens that cause local infection. However, in some settings, the local persistence of memory
T cells that provide robust response is detrimental. TRM are thought to play a key role in local, recurring
inflammatory skin diseases. This proposal seeks to address significant gaps in our understanding of the
mechanisms that regulate cutaneous TRM in health and disease. Defining mechanisms that control TRM
precursor localization and persistence within skin will be important for optimizing vaccines to provide local
protection as well as therapies to prevent unwanted inflammation. Mechanisms that direct the interstitial
migration, persistence and response of cutaneous TRM will be defined in a normal immune response to HSV
infection and in autoimmune vitiligo. While the local cytokine microenvironment is known to direct TRM
formation, factors that inhibit TRM differentiation/persistence are unknown. This proposal will investigate the
hypothesis that depending on the cytokine microenvironment TRM formation is either promoted or inhibited.
Lastly, although TRM have been identified at sites of cutaneous inflammatory disease, targeting TRM is an
untested therapeutic approach. We will use a mouse model of vitiligo with clinical application to investigate the
novel hypothesis that autoreactive TRM maintain depigmentation, and that depletion of autoreactive TRM will
prevent and/or ameliorate disease. Up-regulating pathways that promote the persistence of T cells in
peripheral tissues is a critical focus of current vaccine design; it may be equally important to create approaches
that reverse these pathways to prevent unwanted TRM accumulation within inflamed tissues.
免疫系统必须在最有可能遇到病原体的部位(上皮细胞)保护宿主
屏障器官与宿主环境之间的界限。令人兴奋的最新数据表明
记忆 T 细胞群 (TRM) 长期驻留在外周组织内,并提供第一线宿主
防御引起局部感染的病原体。然而,在某些设置中,内存的本地持久性
提供强烈反应的 T 细胞是有害的。 TRM 被认为在局部、经常性的治疗中发挥着关键作用。
炎症性皮肤病。该提案旨在解决我们对
健康和疾病中调节皮肤 TRM 的机制。定义控制 TRM 的机制
前体在皮肤内的定位和持久性对于优化疫苗以提供局部治疗非常重要
保护以及预防不必要炎症的治疗。引导间隙的机制
皮肤 TRM 的迁移、持久性和反应将在对 HSV 的正常免疫反应中定义
感染和自身免疫性白癜风。虽然已知局部细胞因子微环境可指导 TRM
形成时,抑制 TRM 分化/持续的因素尚不清楚。该提案将调查
假设TRM的形成取决于细胞因子微环境的促进或抑制。
最后,虽然 TRM 已在皮肤炎症性疾病部位被发现,但靶向 TRM 是一种
未经测试的治疗方法。我们将使用具有临床应用的白癜风小鼠模型来研究
新的假设是,自身反应性 TRM 会维持脱色,而自身反应性 TRM 的耗尽会导致色素脱失。
预防和/或改善疾病。上调促进 T 细胞持续存在的途径
外周组织是当前疫苗设计的关键焦点;制定方法可能同样重要
逆转这些途径,防止发炎组织内不必要的 TRM 积累。
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 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
- 批准号:
10624943 - 财政年份:2022
- 资助金额:
$ 41.69万 - 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:
10495217 - 财政年份:2021
- 资助金额:
$ 41.69万 - 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:
$ 41.69万 - 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:
$ 41.69万 - 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:
$ 41.69万 - 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:
$ 41.69万 - 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:
$ 41.69万 - 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:
$ 41.69万 - 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:
$ 41.69万 - 项目类别:
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