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Mechanisms and treatments of autoimmune diseases by Th1/Th2 unbalance

Th1/Th2失衡导致自身免疫性疾病的机制及治疗

基本信息

批准号：
15380210
负责人：
HAYASHI Toshiharu
金额：
$ 8.32万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Summary consisted of 6 items listed bellow concerning mechanisms and treatments of autoimmune diseases by Th1/Th2 unbalance[I].Lupus as Th1 disease : [1].in vivo CpG-ODN-treatment accelerated lupus nephritis during the preactive phase in lupus-prone female NZBxNZWF_1(model) mice, and IL-6 detection in the blood may be an indicator of the onset of the disease. Moreover, IFN-gamma may play a role in IL-6 production. [2].IL-1 and TNF-alfa, which are related to Th1 cytokines, may at least in part be responsible for the increased ICAM-1 expression on endothelium, in cutaneous microvessels, resulting in the vascular injury characterized by neutrophilic lekocytoclasis in B/WF1 mice. [3].CD4^+CD25^+ T cells may, at least in part, downregulate the development of glomerulonephritis during the preactive phase. [II].Type I diabete as Th1 disease. : [1] The systemic administration of IL-4 expressing plasmid DNA inhibited the development of insulitis with impaired glucose tolerance(IGT) in a dose dependent manner. [2]Adhesion molecules(ICAM-1/LFA-1) may be required for the differentiation of Th0 cells to Th1 cwlls, which mediate insulitis with IGT in Reo-2-infected suckling mice.[3].CD4^+CD25^+ T cells may, at least in part,maintain tolerance to Reo-2-triggered and CpG-ODN-induced prolonged mild Th1-depebdent auoimmune insulitis, leading to the overt diabetes.Taken together, the studies suggest that Th2-cytokine expressing plasmid may applicable for a new therapy to lupus as Th1 disease. Moreover our system may give a novel model to elucidate the mechanisms of the development of overt diabetes from borderline diabetes in virus-triggered autoimmune type I diabetes in human.

本文综述了Th 1/Th 2失衡引起的自身免疫性疾病的机制及治疗[I].狼疮作为Th 1型疾病：[1]. CpG-ODN体内处理可加速狼疮易感雌性NZBxNZWF_1（模型）小鼠狼疮性肾炎的前期，血中IL-6的检测可能是狼疮性肾炎发病的一个指标。此外，IFN-γ可能在IL-6产生中起作用。[2].IL-1和TNF-α与Th 1细胞因子相关，可能至少部分地导致B/WF 1小鼠皮肤微血管内皮细胞ICAM-1表达增加，导致以嗜中性白细胞破裂为特征的血管损伤。[3] CD 4 ^+ CD 25 ^+ T细胞可能在活动前期下调肾小球肾炎的发展。[II]. I型糖尿病为Th 1型疾病。[1]全身给予表达IL-4的质粒DNA以剂量依赖的方式抑制糖耐量受损（IGT）的胰岛炎的发展。[2]粘附分子（ICAM-1/LFA-1）可能是Th 0细胞分化为Th 1细胞所必需的，Th 1细胞介导Reo-2感染乳鼠的IGT胰岛炎。[3] CD 4 ^+ CD 25 ^+ T细胞可能对Reo-2和CpG-ODN诱导的持续性轻度Th 1依赖性自身免疫性胰岛炎具有一定的耐受性，从而导致显性糖尿病，提示Th 2-细胞因子表达质粒有望成为治疗狼疮性Th 1疾病的新途径。此外，我们的系统可能会提供一个新的模型，以阐明在病毒触发的自身免疫性I型糖尿病的边缘糖尿病发展为显性糖尿病的机制。