Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
基本信息
- 批准号:10248844
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdoptive ImmunotherapyAdoptive TransferAffectAmericanAnimal ModelAnti-Inflammatory AgentsAntigen TargetingAntigenic SpecificityAntigensAreaAttenuatedAutoimmuneAutoimmune DiseasesAutomobile DrivingCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCNS Demyelinating Autoimmune DiseasesCellsCharacteristicsChronicDataDemyelinating DiseasesDemyelinationsDendritic CellsDevelopmentDiseaseDissectionExhibitsExperimental Autoimmune EncephalomyelitisExperimental ModelsGoalsGranzymeHistologyITGAX geneImmuneImmunizationImmunologicsImmunologyImmunosuppressionImmunotherapeutic agentImmunotherapyInfectionInflammatoryInterferon Type IIInterventionListeria monocytogenesMHC Class I GenesMediatingModelingMolecularMorbidity - disease rateMultiple SclerosisMultiple Sclerosis LesionsMusMyelinNeuraxisOrganPathogenesisPathogenicityPathologyPathway interactionsPeripheralPhenotypePlayPopulationProcessProductionPublishingRecurrent diseaseRegulationRegulatory T-LymphocyteRelapseReportingRoleSJL MouseSignal TransductionSiteT cell responseT-LymphocyteTherapeuticTimeVeteransWorkarmautoreactive T cellautoreactivitybasecentral nervous system demyelinating disordercytotoxiccytotoxicityexperimental studyimmunopathologyimmunoregulationin vivoinnovationinsightmouse modelmultiple sclerosis treatmentneuroinflammationnovelnovel strategiesperforinpreventreceptortraffickingtreatment strategyvaccination strategy
项目摘要
Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS). A
great deal of our understanding about the immunologic processes that underlie MS derives from studies in its
autoimmune animal model, experimental autoimmune encephalomyelitis (EAE). However, the vast majority of
studies in EAE and MS have focused on evaluating and targeting CD4+ T cell responses, with the general
assumption that these diseases are predominantly Th1/Th17-mediated and Th2/Treg-modulated. Recent
reports from others and us indicate that CD8+ T cells play a role in the pathogenesis as well as regulation of
autoimmune demyelination. Our studies in MS and EAE have provided evidence for a novel and
unexpected disease suppressive role for CNS-specific CD8+ T cells (CNS-CD8). Based on our data, we
hypothesize that specific functional and phenotypic subsets of CNS-CD8 form an important and
exploitable arm of immune regulation during autoimmune demyelinating disease. We propose that this
process can be harnessed for the development of effective immunotherapeutic approaches. The
experiments proposed in this application will utilize EAE models to address the fundamental cellular and
molecular mechanisms of immune modulation (IFNγ and its receptor, trafficking and cytotoxicity, suppression
at the site of pathology) by these autoregulatory CD8 T cells, and to define a potent and enhanceable immune
suppressive subset of CNS-CD8. Further, a novel vaccination strategy that reliably engages disease-reversing
CNS-CD8 will also be investigated as a proof of principle. We believe that achievable results from the
proposed experiments will provide greater fundamental insights into CD8 T cell-mediated immune regulation
and pave the way for newer intervention strategies for MS and other immune-mediated diseases.
多发性硬化症 (MS) 是一种中枢神经系统 (CNS) 的炎症性脱髓鞘疾病。
我们对多发性硬化症背后的免疫过程的大部分了解都来自于其研究
自身免疫动物模型,绝大多数是实验性自身免疫性脑脊髓炎(EAE)。
EAE 和 MS 的研究重点是评估和靶向 CD4+ T 细胞反应,一般
假设这些疾病主要是 Th1/Th17 介导的和 Th2/Treg 调节的。
其他人和我们的报告表明 CD8+ T 细胞在发病机制以及调节中发挥作用
我们在 MS 和 EAE 方面的研究为一种新颖且有效的方法提供了证据。
CNS 特异性 CD8+ T 细胞 (CNS-CD8) 具有意想不到的疾病抑制作用。
培养 CNS-CD8 的特定功能和表型子集形成重要且
我们认为,这是自身免疫性脱髓鞘疾病期间可利用的免疫调节手段。
可以利用该过程来开发有效的免疫治疗方法。
本申请中提出的实验将利用 EAE 模型来解决基本的细胞和
免疫调节的分子机制(IFNγ及其受体、运输和细胞毒性、抑制
通过这些自动调节 CD8 T 细胞,并定义有效且可增强的免疫
CNS-CD8 的抑制子集此外,一种可靠地逆转疾病的新型疫苗接种策略。
CNS-CD8 也将作为原理证明进行研究,我们相信可实现的结果。
拟议的实验将为 CD8 T 细胞介导的免疫调节提供更深入的基础见解
并为多发性硬化症和其他免疫介导疾病的新干预策略铺平道路。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
NITIN J KARANDIKAR其他文献
NITIN J KARANDIKAR的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('NITIN J KARANDIKAR', 18)}}的其他基金
Effector-Regulator Immune Interactions During Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病期间效应器-调节器免疫相互作用
- 批准号:
10595509 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Effector-Regulator Immune Interactions During Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病期间效应器-调节器免疫相互作用
- 批准号:
10359998 - 财政年份:2022
- 资助金额:
-- - 项目类别:
ShEEP Request for Cytek Aurora Spectral Flow Cytometer
ShEEP 请求 Cytek Aurora 光谱流式细胞仪
- 批准号:
9905780 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:
9483533 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:
10447061 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
- 批准号:
9338988 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Immune Dysregulation During Multiple Sclerosis Relapse
多发性硬化症复发期间的免疫失调
- 批准号:
9915848 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Immune Dysregulation During Multiple Sclerosis Relapse
多发性硬化症复发期间的免疫失调
- 批准号:
9929670 - 财政年份:2016
- 资助金额:
-- - 项目类别:
CNS-SPECIFIC REGULATORY CD8+ T CELLS IN AUTOIMMUNE DEMYELINATION
CNS 特异性调节 CD8 T 细胞在自身免疫性脱髓鞘中的作用
- 批准号:
8187671 - 财政年份:2011
- 资助金额:
-- - 项目类别:
CNS-Specific Regulatory CD8+ T Cells in Autoimmune Demyelination
CNS 特异性调节 CD8 T 细胞在自身免疫性脱髓鞘中的作用
- 批准号:
8627103 - 财政年份:2011
- 资助金额:
-- - 项目类别:
相似海外基金
Mechanisms of Durable Antitumor Immunity Mediated by PI3K-targeted T cells
PI3K 靶向 T 细胞介导的持久抗肿瘤免疫机制
- 批准号:
10682190 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Hyperpolarized 129Xe MRI for imaging NK cell therapy of lung metastasis
超极化 129Xe MRI 用于肺转移的 NK 细胞治疗成像
- 批准号:
10646013 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Spatial genomic tools to interrogate T cell clonotypes, tumor clones and the microenvironment
用于询问 T 细胞克隆型、肿瘤克隆和微环境的空间基因组工具
- 批准号:
10565141 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Next generation T cell therapies for mutant KRAS solid tumors
针对突变 KRAS 实体瘤的下一代 T 细胞疗法
- 批准号:
10731929 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Modulating the PD-1/PD-L1 checkpoint to promote antitumor activity of HER2 CAR T cells in patients with sarcoma
调节PD-1/PD-L1检查点促进肉瘤患者HER2 CAR T细胞的抗肿瘤活性
- 批准号:
10562836 - 财政年份:2023
- 资助金额:
-- - 项目类别: