Intrathymic Pathogenesis of Myasthenia Gravis
重症肌无力的胸腺内发病机制
基本信息
- 批准号:6740884
- 负责人:
- 金额:$ 31.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-07-01 至 2006-02-14
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): The thymus has been considered to play an
important role in the pathogenesis of myasthenia gravis (MG), a prototypic
autoimmune disease characterized by skeletal muscle weakness. However, its role
still remains a mystery. The expression of the autoantigen, acetylcholine
receptor (AChR), in the thymus has raised the hypothesis that immunity to this
self-protein may be initiated or perhaps perpetuated in this organ. The overall
objective of this proposal is to enhance our understanding of mechanisms by
which an immune response to this self-antigen might be engendered in the
thymus. The hypothesis to be tested is that an inflammatory reaction to an
irrelevant antigen in the thymic medulla leads to augmented entry into the
thymus of peripheral T cells. Included amongst these thymic immigrants are T
cells with low affinity receptors for AChR. Such T cells become activated in
the local milieu of the inflamed thymus where they engage upregulated
expression of AChR, MHC antigens and co-stimulatory molecules on thymic stromal
cells. The Specific Aims of this project are to 1) further characterize our
murine model of thymic inflammation, 2) determine if peripheral T cell
immigration to an inflamed thymus is enhanced relative to a normal thymus, 3)
determine if thymic T cell immigrants are activated by a neo-self-antigen
expressed in an inflamed thymus, and 4) determine if AChR specific T cells
migrate to an inflamed thymus, become activated by locally expressed
autoantigen and initiate a myasthenic syndrome. A retroviral based vector
system will be used to induce thymic inflammation by targeting the expression
of an irrelevant antigen, beta-galactosidase, in the thymic medullary
epithelium of mice immunized to this protein. These studies provide a novel
approach to elucidate the role of the thymus in the pathogenesis of MG.
描述(申请人提供):胸腺被认为是一种
重症肌无力在发病机制中的重要作用
以骨骼肌无力为特征的自身免疫性疾病。然而,它的作用是
这仍然是一个谜。自身抗原乙酰胆碱的表达
胸腺中的受体(AChR),提出了对此免疫的假说
自身蛋白质可能在这个器官中被启动或永久存在。整体而言
这项建议的目的是通过以下方式加强我们对机制的理解
对这种自身抗原的免疫反应可能是在
胸腺。需要检验的假设是,对一种
胸腺髓质中的无关抗原导致进入胸腺
外周T细胞的胸腺。在这些胸腺移居者中包括T
具有低亲和力AChR受体的细胞。这样的T细胞在体内被激活
它们接触的发炎胸腺的局部环境上调
AChR、MHC抗原和共刺激分子在胸腺基质中的表达
细胞。这个项目的具体目标是1)进一步描述我们的
小鼠胸腺炎症模型,2)确定外周T细胞
与正常胸腺相比,炎症胸腺的迁移能力更强。
确定胸腺T细胞移行者是否被新的自身抗原激活
在炎症的胸腺中表达,以及4)确定AChR特异性T细胞
迁移到发炎的胸腺,通过局部表达而激活
自身抗原并引发肌无力综合症。一种基于逆转录病毒的载体
系统将被用于通过靶向表达来诱导胸腺炎症
胸腺髓质中一种无关的抗原--β-半乳糖苷酶
对该蛋白免疫的小鼠上皮细胞。这些研究提供了一种新颖的
探讨胸腺在MG发病机制中的作用。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Intrathymic expression of neuromuscular acetylcholine receptors and the immunpathogenesis of myasthenia gravis.
神经肌肉乙酰胆碱受体的胸腺内表达和重症肌无力的免疫发病机制。
- DOI:10.1385/ir:27:2-3:399
- 发表时间:2003
- 期刊:
- 影响因子:4.4
- 作者:Levinson,ArnoldI;Zheng,Yi;Gaulton,Glen;Song,Decheng;Moore,Jonni;Pletcher,CHank
- 通讯作者:Pletcher,CHank
The intrathymic pathogenesis of myasthenia gravis.
- DOI:10.1080/17402520400001769
- 发表时间:2004-09
- 期刊:
- 影响因子:0
- 作者:Levinson AI;Song D;Gaulton G;Zheng Y
- 通讯作者:Zheng Y
A new model linking intrathymic acetylcholine receptor expression and the pathogenesis of myasthenia gravis.
将胸腺内乙酰胆碱受体表达与重症肌无力发病机制联系起来的新模型。
- DOI:10.1196/annals.1254.027
- 发表时间:2003
- 期刊:
- 影响因子:5.2
- 作者:Levinson,ArnoldI;Zheng,Yi;Gaulton,Glen;Moore,Jonni;Pletcher,CHank;Song,Decheng;Wheatley,LisaM
- 通讯作者:Wheatley,LisaM
Modeling the intrathymic pathogenesis of myasthenia gravis.
模拟重症肌无力的胸腺内发病机制。
- DOI:10.1016/j.jns.2012.12.025
- 发表时间:2013
- 期刊:
- 影响因子:4.4
- 作者:Levinson,ArnoldI
- 通讯作者:Levinson,ArnoldI
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ARNOLD I LEVINSON其他文献
ARNOLD I LEVINSON的其他文献
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{{ truncateString('ARNOLD I LEVINSON', 18)}}的其他基金
B Cell Superantigen Immune Complex Tissue Inflammation
B 细胞超抗原免疫复合物组织炎症
- 批准号:
7179280 - 财政年份:2006
- 资助金额:
$ 31.7万 - 项目类别:
B Cell Superantigen Immune Complex Tissue Inflammation
B 细胞超抗原免疫复合物组织炎症
- 批准号:
7106258 - 财政年份:2006
- 资助金额:
$ 31.7万 - 项目类别:
B Cell Superantigen Immune Complex Tissue Inflammation
B 细胞超抗原免疫复合物组织炎症
- 批准号:
7340459 - 财政年份:2006
- 资助金额:
$ 31.7万 - 项目类别:
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