Tissue-Specific Mechanisms of Regulatory T Cells in the CNS during Autoimmune Encephalomyelitis
自身免疫性脑脊髓炎期间中枢神经系统调节性 T 细胞的组织特异性机制
基本信息
- 批准号:10420232
- 负责人:
- 金额:$ 49.69万
- 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:2022-03-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AblationAntigen PresentationAntigen-Presenting CellsAntigensAreaAutoimmuneAutoimmune DiseasesAutoimmunityAxonBehaviorCNS autoimmunityCalciumCandidate Disease GeneCell SurvivalCell TherapyCell membraneCell physiologyCellsClinical TrialsClonal ExpansionClone CellsCommunicable DiseasesComplexCrowdingCuesDetectionDevelopmentEnsureEnvironmentEvaluationExperimental Autoimmune EncephalomyelitisFailureFunctional disorderGeneticGoalsHealthcareHomeHomeostasisImageImmuneImmune System DiseasesImmune systemImmunosuppressionInfectionInflammationInterleukin-2Ion ChannelKnowledgeLabelLongitudinal StudiesMalignant NeoplasmsMediatingMolecularMonitorMovementMultiple SclerosisMyelinNeuraxisOrganOrgan TransplantationOutcomePathologicPathway interactionsPatternPermeabilityPhasePhysiologicalPiezo 1 ion channelPlayPositioning AttributeProcessProteinsRecoveryRegulatory T-LymphocyteReporterResolutionRoleScanningSignal TransductionSpinal CordSurfaceT-Cell ReceptorTestingTherapeuticTissuesTransgenic MiceVisualizationautoinflammatoryaxon injurybasecell behaviorcell motilitycostexperimental studyfightingfollow-upforkhead proteinimmune imagingimmunological synapseimmunoregulationin vivoinsightlymphoid organmouse modelneuroinflammationpreservationratiometricremyelinationrepairedresponsetargeted treatmenttherapeutic evaluationtherapeutic targettissue repairtwo photon microscopytwo-photon
项目摘要
PROJECT SUMMARY/ABSTRACT
Multiple sclerosis (MS) and other autoimmune diseases constitute a major healthcare burden at a cost of >$125
billion per year. Autoimmune disorders arise from a failure of immunoregulatory networks. Regulatory T (Treg)
cells expressing transcription factor forkhead box protein 3 (Foxp3) are indispensable components of these
networks. Moreover, recent studies from several groups suggest that Treg cells also facilitate tissue repair, in
addition to exerting immunosuppression. During autoimmune diseases, Treg cells are activated in lymphoid
organs and home to non-lymphoid target tissues where they persist in specialized niches to limit inflammation
and facilitate tissue repair. Our overall goal is to determine how these Treg cell niches operate in the central
nervous system (CNS) to ameliorate autoimmune neuroinflammation at cellular and molecular levels. Direct
visualization of cell behavior often leads to surprises, new hypotheses, and follow-up experiments contributing to
a better understanding of the mammalian immune system, and how autoimmunity and infectious diseases can
be effectively treated. Building on our expertise in two-photon (2-P) imaging at the cellular level, and Ca2+
signaling at the molecular level, we will use the experimental autoimmune encephalomyelitis (EAE) mouse model
of MS to: 1) elucidate the local cues that drive survival, functional organization in niches, and motility behaviors
of Treg cells in the spinal cord; 2) investigate how Treg cells selectively target processes that incite
neuroinflammation. Our experimental approach includes evaluation of the Piezo1 channels as promising
therapeutic targets to selectively expand Treg cells, an ideal strategy to curb ongoing autoinflammatory
responses while preserving the immune system’s ability to fight new infections. Although this proposal is targeted
specifically to MS, in a broader context our project will provide fundamental insights into how Treg cells fine-tune
tissue inflammation so that better Treg-modifying therapies can be developed for autoimmune disorders, organ
transplantation, cancer, and infectious diseases.
项目摘要/摘要
多发性硬化症(MS)和其他自身免疫性疾病构成了主要的医疗负担,耗资125美元。
每年10亿美元。自身免疫性疾病是由免疫调节网络的失效引起的。监管T(Treg)
表达转录因子叉头盒蛋白3(Foxp3)的细胞是这些细胞不可缺少的组成部分
网络。此外,几个研究小组最近的研究表明,Treg细胞也有助于组织修复,在
除了施加免疫抑制之外。在自身免疫性疾病期间,Treg细胞在淋巴中被激活
器官和非淋巴靶组织的家,在那里它们坚持在专门的壁龛中限制炎症
并促进组织修复。我们的总体目标是确定这些Treg细胞利基是如何在中央
神经系统(CNS)在细胞和分子水平上改善自身免疫性神经炎症。直接
细胞行为的可视化通常会带来惊喜、新的假设和后续实验,有助于
更好地了解哺乳动物的免疫系统,以及自身免疫和传染病如何
得到有效治疗。基于我们在细胞水平的双光子(2-P)成像方面的专业知识,以及钙离子
在分子水平上,我们将使用实验性自身免疫性脑脊髓炎(EAE)小鼠模型
MS to:1)阐明驱动生存的局部线索、小生境的功能组织和运动行为
2)研究Treg细胞如何选择性地靶向刺激
神经炎。我们的实验方法包括对Piezo1通道进行评估,认为它很有希望
选择性扩增Treg细胞的治疗靶点,这是抑制持续自体炎症的理想策略
在保持免疫系统抵抗新感染的能力的同时做出反应。尽管这项提议是有针对性的
具体地说,在更广泛的背景下,我们的项目将提供有关Treg细胞如何微调的基本见解
组织炎症,从而可以开发更好的Treg修饰疗法来治疗自身免疫性疾病、器官
移植、癌症和传染病。
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 }}
Shivashankar Othy其他文献
Shivashankar Othy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('Shivashankar Othy', 18)}}的其他基金
Tissue-Specific Mechanisms of Regulatory T Cells in the CNS during Autoimmune Encephalomyelitis
自身免疫性脑脊髓炎期间中枢神经系统调节性 T 细胞的组织特异性机制
- 批准号:
10581668 - 财政年份:2022
- 资助金额:
$ 49.69万 - 项目类别:
相似海外基金
Defining MHC class I restricted antigen presentation to CD8 T cells in experimental AD and Tauopathy - Supplement
定义实验性 AD 和 Tau 病中 MHC I 类限制性抗原呈递至 CD8 T 细胞 - 补充
- 批准号:
10836880 - 财政年份:2023
- 资助金额:
$ 49.69万 - 项目类别:
Targeting MAL2-mediated endocytosis to enhance tumor cell antigen presentation
靶向 MAL2 介导的内吞作用以增强肿瘤细胞抗原呈递
- 批准号:
10734324 - 财政年份:2023
- 资助金额:
$ 49.69万 - 项目类别:
Antigen presentation to the adaptive immune system in the choroid contributes to ocular autoimmune disease
脉络膜中的适应性免疫系统的抗原呈递导致眼部自身免疫性疾病
- 批准号:
10740465 - 财政年份:2023
- 资助金额:
$ 49.69万 - 项目类别:
Investigation of Target Protein Degradation and Its Effect on Enhancing Cancer-Specific Antigen Presentation by Quantitative Mass Spectrometry
通过定量质谱研究靶蛋白降解及其对增强癌症特异性抗原呈递的影响
- 批准号:
23K04971 - 财政年份:2023
- 资助金额:
$ 49.69万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Promoting cancer cells' antigen presentation for serving as better targets for T cell immunotherapy
促进癌细胞的抗原呈递,作为 T 细胞免疫治疗的更好靶点
- 批准号:
2885451 - 财政年份:2023
- 资助金额:
$ 49.69万 - 项目类别:
Studentship
Targeting immunoproteasome-mediated antigen presentation in colorectal cancer immunotherapy
结直肠癌免疫治疗中靶向免疫蛋白酶体介导的抗原呈递
- 批准号:
10385926 - 财政年份:2022
- 资助金额:
$ 49.69万 - 项目类别:
Lipid Antigen Presentation as a Driver of T2D Inflammation
脂质抗原呈递作为 T2D 炎症的驱动因素
- 批准号:
10509043 - 财政年份:2022
- 资助金额:
$ 49.69万 - 项目类别:
Enhancing antigen presentation in triple negative breast cancers through CD40 agonist, Flt3 ligand, and anthracycline chemotherapy
通过 CD40 激动剂、Flt3 配体和蒽环类化疗增强三阴性乳腺癌的抗原呈递
- 批准号:
10704008 - 财政年份:2022
- 资助金额:
$ 49.69万 - 项目类别:
Sex Differences in lipid antigen presentation, impact of lipid antigen presentation on peripheral lipid metabolism
脂质抗原呈递的性别差异,脂质抗原呈递对外周脂质代谢的影响
- 批准号:
10818273 - 财政年份:2022
- 资助金额:
$ 49.69万 - 项目类别:
Enhancing antigen presentation in triple negative breast cancers through CD40 agonist, Flt3 ligand, and anthracycline chemotherapy
通过 CD40 激动剂、Flt3 配体和蒽环类化疗增强三阴性乳腺癌的抗原呈递
- 批准号:
10349397 - 财政年份:2022
- 资助金额:
$ 49.69万 - 项目类别: