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地方--上皮细胞--保护宿主。
屏障器官和宿主环境之间的边界。最近令人兴奋的数据表明,
记忆T细胞群(TRM)长期驻留在外周组织中,并提供第一宿主
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
提供强健反应的T细胞是有害的。TRM被认为在局部、复发的
炎症性皮肤病。这项建议旨在解决我们对
在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
保护和治疗,以防止不必要的炎症。引导组织间隙的机制
皮肤TRM的迁移、持久性和反应将被定义为对HSV的正常免疫反应
感染和自身免疫性白癜风。而已知的局部细胞因子微环境指导着TRM
形成,抑制TRM分化/持久性的因素尚不清楚。这项提案将调查
根据细胞因子微环境的不同,TRM的形成要么被促进,要么被抑制。
最后,尽管已经在皮肤炎性疾病部位发现了TRM,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
新的假设认为,自身反应性TRM维持色素脱失,而自身反应性TRM的耗尽将
预防和/或改善疾病。上调促进T细胞在体内持续存在的途径
外周组织是当前疫苗设计的一个关键焦点;创造方法可能同样重要
逆转这些途径,以防止不必要的TRM在炎症组织中积聚。
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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