Regulation of Th17 Functions in Autoimmune CNS Inflammation
自身免疫性中枢神经系统炎症中 Th17 功能的调节
基本信息
- 批准号:9177748
- 负责人:
- 金额:$ 38.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-12-01 至 2019-11-30
- 项目状态:已结题
- 来源:
- 关键词:AdhesionsAdverse effectsAffectAmericanAutoimmune DiseasesAutoimmune Diseases of the Nervous SystemAutoimmune ProcessAutomobile DrivingBiological AssayBloodBlood VesselsBone MarrowBrainCandidiasisCell physiologyCellsChemicalsChimera organismDangerousnessDataDevelopmentDiseaseEffector CellEndothelial CellsExperimental Autoimmune EncephalomyelitisExtracellular MatrixGoalsHumanITGB3 geneIn VitroInfectionInflammationInflammatoryIntegrinsInterleukin-17Interleukin-6InvestigationLeadLigandsLigationMediatingMigration AssayModelingMolecularMultiple SclerosisMultiple Sclerosis LesionsMusMyelogenousOral mucous membrane structurePTK2 genePathogenesisPathway interactionsPatientsPharmaceutical PreparationsPhysiologicalPredispositionProductionPublishingRegulationReportingRiskRoleSTAT3 geneSignal PathwaySignal TransductionSliceSystemT-LymphocyteTestingTissuesTreatment EfficacyWorkangiogenesisbasecell motilitychronic autoimmune diseasecytokinein vivointerleukin-23live cell imagingmigrationmouse modelmultiple sclerosis patientnew therapeutic targetnovelosteopontinpublic health relevancereceptorreconstitutionresponsetherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Multiple Sclerosis (MS) is a debilitating autoimmune neurological disease. Th17 cells have emerged as key drivers of pathogenesis in chronic autoimmune disease and are increased in MS patients. Th17 cells are also critical for driving CNS inflammation in the murine model of MS, experimental autoimmune encephalomyelitis (EAE). Our previous work demonstrated that Th17 cells are dependent on signals from IL-23 for their proliferation and differentiation into effector cells capable of driving inflammation in EAE.
Although Th17 cells are mostly considered as IL-17 producers, they have many additional functions and IL-17 is not always sufficient to drive disease. However, IL-23 is critical, and our goal is to understand the specific mechanisms by which IL-23 promotes Th17 functions in inflammatory disease. We have recently discovered a novel integrin that is expressed by effector Th17 cells in an IL-23-dependent manner, and required for EAE. Published reports describe increased expression of this integrin in a number of human inflammatory diseases, including MS. However, almost nothing is known about its functional importance in T cells, and in particular Th17 cells. Collectively, these data form the basis for our central hypothesis that this integrin is a key IL-23-driven molecule involved in determining the inflammatory activity of autoimmune Th17 cells. We now aim to interrogate the role of its expression in Th17-mediated inflammation, and thereby to validate this integrin as a novel Th17-directed therapeutic target.
描述(由申请人提供):多发性硬化症(MS)是一种使人衰弱的自身免疫性神经系统疾病。Th17细胞已成为慢性自身免疫性疾病发病机制的关键驱动因素,并在MS患者中增加。在多发性硬化症(实验性自身免疫性脑脊髓炎(EAE))小鼠模型中,Th17细胞也是驱动中枢神经系统炎症的关键细胞。我们之前的研究表明,Th17细胞依赖于IL-23的信号来增殖和分化为能够驱动EAE炎症的效应细胞。
项目成果
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Mandy J McGeachy其他文献
GM-CSF: the secret weapon in the TH17 arsenal
GM-CSF:TH17 武库中的秘密武器
- DOI:
10.1038/ni.2044 - 发表时间:
2011-05-18 - 期刊:
- 影响因子:27.600
- 作者:
Mandy J McGeachy - 通讯作者:
Mandy J McGeachy
Mandy J McGeachy的其他文献
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{{ truncateString('Mandy J McGeachy', 18)}}的其他基金
IL-17 regulation of type-1 immunity in chronic viral infection
IL-17 对慢性病毒感染中 1 型免疫的调节
- 批准号:
10736692 - 财政年份:2022
- 资助金额:
$ 38.12万 - 项目类别:
IL-17 regulation of type-1 immunity in chronic viral infection
IL-17 对慢性病毒感染中 1 型免疫的调节
- 批准号:
10641910 - 财政年份:2022
- 资助金额:
$ 38.12万 - 项目类别:
IL-17 regulates LN stromal cell metabolism and function
IL-17 调节 LN 基质细胞代谢和功能
- 批准号:
10535446 - 财政年份:2020
- 资助金额:
$ 38.12万 - 项目类别:
IL-17 regulates LN stromal cell metabolism and function
IL-17 调节 LN 基质细胞代谢和功能
- 批准号:
10643128 - 财政年份:2020
- 资助金额:
$ 38.12万 - 项目类别:
IL-17 regulates LN stromal cell metabolism and function
IL-17 调节 LN 基质细胞代谢和功能
- 批准号:
10318971 - 财政年份:2020
- 资助金额:
$ 38.12万 - 项目类别:
Regulation of Th17 Functions in Autoimmune CNS Inflammation
自身免疫性中枢神经系统炎症中 Th17 功能的调节
- 批准号:
8962148 - 财政年份:2014
- 资助金额:
$ 38.12万 - 项目类别:
Regulation of Th17 Functions in Autoimmune CNS Inflammation
自身免疫性中枢神经系统炎症中 Th17 功能的调节
- 批准号:
8825305 - 财政年份:2014
- 资助金额:
$ 38.12万 - 项目类别:
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