Regulatory Mechanisms in Autoimmune Arthritis
自身免疫性关节炎的调节机制
基本信息
- 批准号:8597917
- 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:2012
- 资助国家:美国
- 起止时间:2012-10-01 至 2016-09-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnimal ModelAntigensArthritisAutoimmune DiseasesAutoimmune ProcessAutoimmune ResponsesAutoimmunityCartilageCellsCharacteristicsClinicCollagenCollagen ArthritisComplement Factor BComplexDevelopmentDiseaseDisease remissionEmployee StrikesEtiologyExposure toGreen Fluorescent ProteinsHomeostasisHumanImmuneImmune responseImmune systemIn VitroInflammationInflammation MediatorsInflammatoryInterleukin-17Interleukin-6InterruptionJointsLabelLigandsMeasuresMediatingModalityModelingMusNatureParticipantPathogenesisPathologicPathologyPathway interactionsPatientsPhenotypePlayPopulationPredispositionPreventionProcessQuality of lifeReactionRegulationRegulatory T-LymphocyteReporterResearchResearch Project GrantsResistanceRheumatoid ArthritisRoleSeveritiesSignal TransductionSynovial FluidSystemT-LymphocyteTherapeuticTransforming Growth FactorsTransgenic OrganismsTranslatingVeteransWorkautoimmune arthritisbasebonecell typedesignhuman leukocyte antigen geneimmunoregulationin vivoin vivo Modelinterestjoint functionjoint injurylymph nodesnovel therapeutic interventionprecursor cellpreventpromoterred fluorescent proteinresponsetool
项目摘要
DESCRIPTION (provided by applicant):
Rheumatoid arthritis (RA) is a crippling disease afflicting millions of people worldwide. Its progressive, destructive pathology significantly affects mobility and quality of life. RA is a complex disease process that involves the interaction of HLA molecules and immune cells that results in synovial inflammation, cartilage and bone destruction, and loss of joint function. Although its etiology is still a mystery, it is clear that there is a strong association between susceptibility to RA and the HLA genes that mediate immune responses, suggesting an autoimmune basis for the disease. Regulatory T cells (Tregs) are a newly described subset of suppressive cells that are absolutely critical for immune homeostasis. Without a proper compliment of Tregs, multiple forms of autoimmunity develop quickly. It is clear that Tregs can modulate autoimmunity, but there are large gaps in our understanding of how Tregs function in vivo, and how they can be manipulated for the development of new therapeutic approaches to the treatment of autoimmune diseases. We will use a Foxp3gfp/IL-17Frfp dual reporter readout in the context of our well- characterized animal model for arthritis to give us a unique opportunit to dissect the role of Treg cells in autoimmunity, allowing us to directly examine the ability of these cells to regulate an autoimmune response and we can directly measure how these manipulations can prevent disease pathology. Our research to date has suggested that parenteral exposure of the vertebrate immune system to a soluble antigen supplied without co-stimulation can result in an activation and expansion of a pre-existing population of regulatory T cells. It is our hypothesis that this activation provides the commitment necessary to prevent the possible conversion of these nTregs into Th17 cells upon subsequent exposure to their cognate ligand under pro-inflammatory conditions such as those found in the rheumatoid joint. We propose to use both in vitro and in vivo models to determine the mechanism(s) by which parenteral antigen induced immunoregulation prevents the development of the Th17 cell response, thereby providing protection from the debilitating joint pathologies characteristic of RA. We will also determine if the proper stimulation of Tregs can prevent them from converting to Th17 cells in the presence of pro-inflammatory mediators. Successful elucidation of the answers to these problems will allow us to design cell-based therapeutic treatments for those veterans suffering from the debilitating effects of RA and other inflammatory autoimmune diseases.
描述(由申请人提供):
类风湿性关节炎(RA)是一种严重的疾病,困扰着全世界数百万人。其进行性、破坏性病理学显着影响活动能力和生活质量。 RA 是一种复杂的疾病过程,涉及 HLA 分子和免疫细胞的相互作用,导致滑膜炎症、软骨和骨骼破坏以及关节功能丧失。尽管其病因仍是一个谜,但很明显,RA 易感性与介导免疫反应的 HLA 基因之间存在密切关联,表明该疾病存在自身免疫基础。调节性 T 细胞 (Treg) 是一种新近描述的抑制性细胞子集,对于免疫稳态至关重要。如果没有适当的调节性T细胞,多种形式的自身免疫就会迅速发展。很明显,Tregs 可以调节自身免疫,但我们对 Tregs 在体内如何发挥作用,以及如何操纵它们来开发治疗自身免疫性疾病的新治疗方法的理解还存在很大差距。我们将在我们明确表征的关节炎动物模型中使用 Foxp3gfp/IL-17Frfp 双报告读数,为我们提供独特的机会来剖析 Treg 细胞在自身免疫中的作用,使我们能够直接检查这些细胞的能力调节自身免疫反应,我们可以直接测量这些操作如何预防疾病病理。我们迄今为止的研究表明,在没有共刺激的情况下,脊椎动物免疫系统肠外暴露于可溶性抗原,可以导致预先存在的调节性 T 细胞群的激活和扩增。我们的假设是,这种激活提供了必要的承诺,以防止这些 nTreg 在随后暴露于促炎条件(例如类风湿关节中发现的条件)下的同源配体时可能转化为 Th17 细胞。我们建议使用体外和体内模型来确定肠外抗原诱导的免疫调节阻止 Th17 细胞反应发展的机制,从而提供针对 RA 衰弱性关节病理特征的保护。我们还将确定在促炎介质存在的情况下,适当刺激 Tregs 是否可以阻止它们转化为 Th17 细胞。成功阐明这些问题的答案将使我们能够为那些患有类风湿性关节炎和其他炎症性自身免疫性疾病的退伍军人设计基于细胞的治疗方法。
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 }}
DAVID D. BRAND其他文献
DAVID D. BRAND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('DAVID D. BRAND', 18)}}的其他基金
Elucidating the Mechanisms that link the Shared Epitope, Periodontal Disease and Arthritis
阐明共享表位、牙周病和关节炎之间的联系机制
- 批准号:
9352706 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Elucidating the Mechanisms that link the Shared Epitope, Periodontal Disease and Arthritis
阐明共享表位、牙周病和关节炎之间的联系机制
- 批准号:
9898304 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Program Project for Mechanisms and Treatment of Arthritis
关节炎的机制和治疗计划项目
- 批准号:
8598790 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Program Project for Mechanisms and Treatment of Arthritis
关节炎的机制和治疗计划项目
- 批准号:
8246345 - 财政年份:2012
- 资助金额:
-- - 项目类别:
GENETIC SUSCEPTIBILITY TO COLLAGEN INDUCED ARTHRITIS
对胶原蛋白引起的关节炎的遗传易感性
- 批准号:
2078077 - 财政年份:1994
- 资助金额:
-- - 项目类别:
GENETIC SUSCEPTIBILITY TO COLLAGEN INDUCED ARTHRITIS
对胶原蛋白引起的关节炎的遗传易感性
- 批准号:
2078076 - 财政年份:1993
- 资助金额:
-- - 项目类别:
相似国自然基金
肾—骨应答调控骨骼VDR/RXR对糖尿病肾病动物模型FGF23分泌的影响及中药的干预作用
- 批准号:82074395
- 批准年份:2020
- 资助金额:55 万元
- 项目类别:面上项目
基于细胞自噬调控的苦参碱对多囊肾小鼠动物模型肾囊肿形成的影响和机制研究
- 批准号:
- 批准年份:2019
- 资助金额:33 万元
- 项目类别:地区科学基金项目
靶向诱导merlin/p53协同性亚细胞穿梭对听神经瘤在体生长的影响
- 批准号:81800898
- 批准年份:2018
- 资助金额:21.0 万元
- 项目类别:青年科学基金项目
伪狂犬病病毒激活三叉神经节细胞对其NF-кB和PI3K/Akt信号转导通路影响的分子机制研究
- 批准号:31860716
- 批准年份:2018
- 资助金额:39.0 万元
- 项目类别:地区科学基金项目
基于中枢胰岛素抵抗探讨自噬失调对肾虚阿尔茨海默的影响及机制研究
- 批准号:81803854
- 批准年份:2018
- 资助金额:21.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Endothelial Cell Reprogramming in Familial Intracranial Aneurysm
家族性颅内动脉瘤的内皮细胞重编程
- 批准号:
10595404 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Dravet Syndrome Anti-Epileptic Control by Targeting GIRK Channels
通过针对 GIRK 通道进行 Dravet 综合征抗癫痫控制
- 批准号:
10638439 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Novel application of pharmaceutical AMD3100 to reduce risk in opioid use disorder: investigations of a causal relationship between CXCR4 expression and addiction vulnerability
药物 AMD3100 降低阿片类药物使用障碍风险的新应用:CXCR4 表达与成瘾脆弱性之间因果关系的研究
- 批准号:
10678062 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Mechanisms of Metal Ion Homeostasis of Oral Streptococci
口腔链球菌金属离子稳态机制
- 批准号:
10680956 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Design and testing of a novel circumesophageal cuff for chronic bilateral subdiaphragmatic vagal nerve stimulation (sVNS)
用于慢性双侧膈下迷走神经刺激(sVNS)的新型环食管套囊的设计和测试
- 批准号:
10702126 - 财政年份:2023
- 资助金额:
-- - 项目类别: