SELECTIN IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

实验性过敏性脑脊髓炎中的选择素

• 批准号: 6340671
• 负责人: Richard A. Flavell
• 金额: $ 13.33万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340671
• 关键词: T lymphocyte; astrocytes; autoimmunity; blood brain barrier; disease /disorder model; experimental allergic encephalomyelitis; gene expression; genetically modified animals; histology; immunocytochemistry; immunoregulation; laboratory mouse; macrophage; molecular pathology; multiple sclerosis; neutrophil; passive immunization; pathologic process; selectins; tumor necrosis factor alpha

Experimental allergic encephalomyelitis (EAE) is a model for the human autoimmune disease multiple sclerosis, and results from the activation of myelin-reactive CD4 T cells. The mechanisms underlying this disease model are poorly understood. Selectins play a key role in the entry of lymphocytes into lymphoid organs where priming of autoreactive T- lymphocytes takes place, and leukocytes to sites of inflammation where tissue destruction occurs in autoimmunity. We will employ selectin- deficient mice to determine the role of these molecules in EAE. Our preliminary data show that L-selectin is required for EAE to develop. We will determine the nature of the L-selectin deficiently in EAE and upon which cell populations L-selectin must be expressed for disease. We will further specificity determine whether L-selectin is required for the entry of inflammatory cells into the CNS or for the effector mechanisms of tissue destruction within the CNS. Finally, we will determine whether endothelial selectins (E/P selectins) are required for EAE, and if so, why.

实验性变态反应性脑脊髓炎（EAE）是人类的一种模型， 自身免疫性疾病多发性硬化症，并导致激活 髓鞘反应性CD 4 T细胞。这种疾病模型的潜在机制 我们对此知之甚少。选择素在进入 淋巴细胞进入淋巴器官，在那里引发自身反应性T- 淋巴细胞和白细胞转移到炎症部位， 组织破坏发生在自身免疫中。我们会选择- 缺陷小鼠，以确定这些分子在EAE中的作用。我们 初步数据显示L-选择素是EAE发展所必需的。我们 将确定EAE中L-选择素缺乏的性质， 哪些细胞群体的L-选择素必须表达才能致病。我们将 进一步的特异性决定是否需要L-选择素进入 炎症细胞进入中枢神经系统或为效应机制， CNS内的组织破坏。最后，我们将确定 内皮选择素（E/P选择素）是EAE所必需的，如果是这样， 为什么.