Exocrine Gland Targeting in Autoimmune NOD Mice
自身免疫 NOD 小鼠的外分泌腺靶向
基本信息
- 批准号:6524233
- 负责人:
- 金额:$ 25.74万
- 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:2001-08-01 至 2006-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Sjogren's syndrome, one of the connective
tissue autoimmune diseases, presents clinically as a loss of exocrine secretory
function due to autoaggression primarily against the salivary and lacrimal
glands. The mechanism(s) underlying the tissue specific destruction of target
organs in Sjogren's syndrome is not understood at the present time. Our studies
have now established the NOD (non-obese diabetic) and NOD.B10.H2b mice as the
best animal models for secondary and primary Sjogren's syndrome, respectively.
To date, the NOD mouse remains the only animal identified to develop the
corresponding pathophysiology of salivary gland secretion loss and lacrimal
tear production in conjunction with the histological observation of lymphocytic
infiltration of the exocrine tissues. Results of our studies have novel
implications in how we define the autoimmune disease paradigm with the
observation of exocrine gland cellular alterations which develop in the absence
of a functional lymphocyte system (NOD-scid). Autoimmune diseases, such as
IDDM, IBD, and Hashimoto's thyroiditis, similar to our studies in both the
NOD-scid and NOD parental strain, indicate nonimmune factors, as a consequence
of genetically programmed loss of glandular differentiated function or
homeostasis, appear to contribute to initiating the disease process. Using a
second congenic strain lacking B-cells (NOD.Igu null), the loss of secretory
function was shown to be independent of T-cells but not autoantibodies. To
elucidate further the mechanism(s) responsible for the loss of exocrine target
tissue function of Sjogren' s syndrome-like disease in the NOD model, the
following specific aims are proposed: 1. Define the role of regulatory effector
cytokines modulating the humoral response in autoimmune exocrinopathy through
the analysis of specific knockout mice; and 2. Define the components of the
humoral immune response promoting exocrine gland destruction, using the NOD
mouse models of Sjogren's syndrome. These studies will expand on our novel
observations which established the NOD mouse as an appropriate model for the
study of Sjogren's syndrome-like pathology by analyzing the role of the humoral
immune system components and effector cytokines in the precipitation of
exocrine tissue dysfunction. By using a global approach to the analyses of this
autoimmune disease involving a coordinated evaluation of both the lacrimal and
salivary glands, the results from this research will provide innovative
insights into the mechanism(s) triggering autoimmune attack on specific tissues
and further suggest novel strategies for the control of this tissue
destruction.
描述(由申请人提供):干燥综合征,结缔组织疾病之一,
组织自身免疫性疾病,临床上表现为外分泌分泌功能丧失,
由于主要针对唾液和泪腺的自身攻击而产生的功能
腺体靶组织特异性破坏的潜在机制
目前尚不清楚干燥综合征中的器官。我们的研究
现在已经建立了NOD(非肥胖糖尿病)和NOD.B10.H2b小鼠作为
继发性和原发性干燥综合征的最佳动物模型。
到目前为止,NOD小鼠仍然是唯一被鉴定为发展成
唾液腺分泌减少和泪腺分泌减少的相应病理生理学
泪液生成与淋巴细胞的组织学观察相结合
外分泌组织的浸润。我们的研究结果具有新颖性
在我们如何定义自身免疫性疾病的范例与影响,
观察外分泌腺细胞的变化,
功能性淋巴细胞系统(NOD-scid)。自身免疫性疾病如
IDDM、IBD和桥本甲状腺炎,与我们在两组中的研究相似。
NOD-scid和NOD亲本菌株,表明非免疫因素,因此,
腺分化功能的遗传程序性丧失,或
体内平衡,似乎有助于启动疾病过程。使用
第二个同源株缺乏B细胞(NOD.Igu null),分泌功能丧失,
功能显示不依赖于T细胞,但不依赖于自身抗体。到
进一步阐明外分泌靶点丢失的机制
NOD模型中干燥综合征样疾病的组织功能,
提出了以下具体目标:1.定义调节效应器的作用
通过细胞因子调节自身免疫性外分泌体病的体液反应
特异性基因敲除小鼠的分析;和2.定义的组件
使用NOD的促进外分泌腺破坏的体液免疫应答
干燥综合征的小鼠模型。这些研究将扩展我们的小说
这些观察结果将NOD小鼠确立为研究
体液免疫在干燥综合征样病理中的作用
免疫系统成分和效应细胞因子的沉淀,
外分泌组织功能障碍通过使用全球方法来分析这一问题,
自身免疫性疾病涉及泪腺和
唾液腺,这项研究的结果将提供创新的
对触发特定组织自身免疫攻击的机制的见解
并进一步提出了控制这种组织的新策略
杀伤性
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('AMMON B PECK', 18)}}的其他基金
Gene therapy targeting the Th17 / IL-27 system in autoimmune exocrinopathy
针对自身免疫性外分泌病的 Th17/IL-27 系统基因治疗
- 批准号:
7634844 - 财政年份:2009
- 资助金额:
$ 25.74万 - 项目类别:
Gene therapy targeting the Th17 / IL-27 system in autoimmune exocrinopathy
针对自身免疫性外分泌病的 Th17/IL-27 系统基因治疗
- 批准号:
7895693 - 财政年份:2009
- 资助金额:
$ 25.74万 - 项目类别:
Oxalobacter as a therapy in IBD-associated urolithiasis
草酸杆菌作为 IBD 相关尿石症的治疗方法
- 批准号:
6862101 - 财政年份:2005
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$ 25.74万 - 项目类别:
Oxalobacter as a therapy in IBD-associated urolithiasis
草酸杆菌作为 IBD 相关尿石症的治疗方法
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7031596 - 财政年份:2005
- 资助金额:
$ 25.74万 - 项目类别:
IN VITRO DIFFERENTIATION OF CORD BLOOD STEM CELLS INTO ENDOCRINE PANCREAS FOR I
脐带血干细胞体外分化为内分泌胰腺
- 批准号:
7202933 - 财政年份:2004
- 资助金额:
$ 25.74万 - 项目类别:
Genetic Control of Autoimmune Exocrinopathy in NOD Mice
NOD 小鼠自身免疫性外分泌病的遗传控制
- 批准号:
6574886 - 财政年份:2003
- 资助金额:
$ 25.74万 - 项目类别:
Genetic Control of Autoimmune Exocrinopathy in NOD Mice
NOD 小鼠自身免疫性外分泌病的遗传控制
- 批准号:
6737582 - 财政年份:2003
- 资助金额:
$ 25.74万 - 项目类别:
Genetic Control of Autoimmune Exocrinopathy in NOD Mice
NOD 小鼠自身免疫性外分泌病的遗传控制
- 批准号:
7216252 - 财政年份:2003
- 资助金额:
$ 25.74万 - 项目类别:
IL-4 Signaling Pathway Regulation of Sjogren's Syndrome
IL-4 信号通路对干燥综合征的调节
- 批准号:
6601460 - 财政年份:2003
- 资助金额:
$ 25.74万 - 项目类别:
IL-4 Signaling Pathway Regulation of Sjogren's Syndrome
IL-4 信号通路对干燥综合征的调节
- 批准号:
6744101 - 财政年份:2003
- 资助金额:
$ 25.74万 - 项目类别:
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