New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis
补体调节实验性自身免疫性葡萄膜炎发病机制的新机制
基本信息
- 批准号:10397686
- 负责人:
- 金额:$ 39.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:Active ImmunizationAdoptive TransferAntigen-Presenting CellsApoptosisArrestinsBlindnessBlood-Retinal BarrierC3AR1 geneCD55 AntigensCell membraneCell physiologyCellsClinicalComplementComplement 3aComplement 5aComplement ActivationComplement InactivatorsComplement ReceptorDataDendritic CellsDendritic cell activationDevelopmentDiseaseDisease remissionEtiologyEyeFOXP3 geneFoundationsFutureGenerationsHumanIn VitroInflammationInnate Immune SystemKnock-outKnockout MiceLipid BilayersLipidsMediatingModelingMusNaturePathogenesisPathogenicityPathologicPatientsPeripheralPermeabilityProductionProteinsPublishingRattusReagentRecombinantsRegulationRegulatory T-LymphocyteRelapseRetinaRodent ControlRoleSignal TransductionSolidSurfaceT cell responseT-Cell ActivationT-LymphocyteTailTestingTherapeuticTissuesTransgenic MiceTumor-infiltrating immune cellsWorkantagonistantigen-specific T cellsautoimmune pathogenesisautoimmune uveitisautoreactive T cellcell motilityclinical developmentcytokineeffective therapyeffector T cellefficacy evaluationefficacy testingexperimental studyimprovedin vivoinhibitorinterstitial retinol-binding proteinknockout genemigrationmonolayermouse modelnanoparticlenew therapeutic targetnovelnovel therapeuticspreventreceptorrecruittargeted treatmenttranslational study
项目摘要
Abstract
Autoimmune uveitis, a common cause of blindness, has an unknown etiology and no known cure. We
have been studying experimental autoimmune uveitis (EAU) induced in mice deficient in various complement
components, inhibitors, or receptors following active immunization with a retinal antigen and the adoptive transfer
of already primed retinal antigen-specific T cells. Our findings strongly suggest that complement, particularly the
complement receptors C3aR and C5aR, are required for not only the priming of autoreactive T cells in the
periphery, but also the migration and/or re-stimulation of already activated pathogenic T cells in the retina. These
findings suggest that these complement receptors could be new therapeutic targets for treating EAU and,
eventually, autoimmune uveitis.
In this proposed work, we will focus on the previously unknown role of complement in regulating the
migration and/or re-stimulation of already primed autoreactive T cells in a target tissue, using EAU as a model.
We will also elucidate the underlying mechanisms using various systemic and cell-specific complement-related
gene knockout mice and other novel reagents. In addition, we will examine the efficacies and investigate the
underlying mechanisms of our novel complement-targeted reagents for suppressing the migration and re-
stimulation of previously activated uveitogenic T cells in the retina for the treatment of EAU both in mice and in
rats. These studies will significantly improve our understanding of the pathogenesis of autoimmune uveitis and
facilitate the development of novel complement-targeted therapeutics for the treatment of this blinding disease.
摘要
自身免疫性葡萄膜炎是一种常见的致盲原因,其病因不明,也没有已知的治疗方法。我们
一直在研究实验性自身免疫性葡萄膜炎(EAU)诱导的小鼠缺乏各种补体
在用视网膜抗原主动免疫和过继转移后,
视网膜抗原特异性T细胞我们的研究结果强烈表明,补充,特别是
补体受体C3 aR和C5 aR不仅是在免疫系统中引发自身反应性T细胞所必需的,
这不仅可以促进外周的免疫反应,而且还可以促进视网膜中已经活化的致病性T细胞的迁移和/或再刺激。这些
研究结果表明,这些补体受体可能成为治疗EAU的新治疗靶点,
最终导致自身免疫性葡萄膜炎
在这项拟议的工作中,我们将重点放在以前未知的作用,补体在调节
已经引发的自身反应性T细胞在靶组织中的迁移和/或再刺激,使用EAU作为模型。
我们还将阐明潜在的机制,使用各种系统性和细胞特异性补体相关的,
基因敲除小鼠和其他新试剂。此外,我们将检验疗效,并调查
我们的新型补体靶向试剂用于抑制迁移和再
刺激视网膜中先前活化的葡萄膜原性T细胞用于治疗小鼠和小鼠中的EAU。
大鼠这些研究将显著提高我们对自身免疫性葡萄膜炎发病机制的认识,
有助于开发用于治疗这种致盲性疾病的新型补体靶向治疗剂。
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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{{ truncateString('FENG C LIN', 18)}}的其他基金
Role of CDCP1 in the pathogenesis of autoimmune uveitis
CDCP1在自身免疫性葡萄膜炎发病机制中的作用
- 批准号:
10655755 - 财政年份:2023
- 资助金额:
$ 39.04万 - 项目类别:
Development of a novel antibody-drug conjugate for treating T-cell lymphoma.
开发用于治疗 T 细胞淋巴瘤的新型抗体-药物缀合物。
- 批准号:
10545523 - 财政年份:2022
- 资助金额:
$ 39.04万 - 项目类别:
Development of a new drug for treating autoimmune uveitis
治疗自身免疫性葡萄膜炎新药的研制
- 批准号:
10321980 - 财政年份:2021
- 资助金额:
$ 39.04万 - 项目类别:
New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis
补体调节实验性自身免疫性葡萄膜炎发病机制的新机制
- 批准号:
10175270 - 财政年份:2021
- 资助金额:
$ 39.04万 - 项目类别:
New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis
补体调节实验性自身免疫性葡萄膜炎发病机制的新机制
- 批准号:
10619536 - 财政年份:2021
- 资助金额:
$ 39.04万 - 项目类别:
A novel regulator of Pseudomonas aeruginosa keratitis
铜绿假单胞菌角膜炎的新型调节剂
- 批准号:
10618396 - 财政年份:2020
- 资助金额:
$ 39.04万 - 项目类别:
A novel regulator of Pseudomonas aeruginosa keratitis
铜绿假单胞菌角膜炎的新型调节剂
- 批准号:
10401830 - 财政年份:2020
- 资助金额:
$ 39.04万 - 项目类别:
A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitis
角膜伤口愈合和铜绿假单胞菌角膜炎的新型调节剂
- 批准号:
9898378 - 财政年份:2019
- 资助金额:
$ 39.04万 - 项目类别:
A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitis
角膜伤口愈合和铜绿假单胞菌角膜炎的新型调节剂
- 批准号:
10391450 - 财政年份:2019
- 资助金额:
$ 39.04万 - 项目类别:
A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitis
角膜伤口愈合和铜绿假单胞菌角膜炎的新型调节剂
- 批准号:
10133084 - 财政年份:2019
- 资助金额:
$ 39.04万 - 项目类别:
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