Chemokine IP-10 and Viral-Induced Demyelination
趋化因子 IP-10 和病毒引起的脱髓鞘
基本信息
- 批准号:6657924
- 负责人:
- 金额:$ 18.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-04-01 至 2008-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Infection of susceptible mice with mouse hepatitis virus (JHMV, a positive-strand RNA virus) results in an acute encephalomyelitis following by a chronic demyelinating disease that shares many similarities with the human demyelinating disease Multiple Sclerosis (MS). Animals develop ascending hind-limb paralysis accompanied by mononuclear cell infiltration into the central nervous system (CNS) and myelin destruction. As such, the JMHV model of demyelination is a well accepted model to study the immunopathological mechanisms contributing to human demyelinating diseases such as MS. T cells and macrophages are considered important contributors to JHMV-induced demyelination as well as demyelination in MS patients. The long-range goal of this proposal is to better understand the molecular mechanisms governing the trafficking and entry of T cells into the CNS following JMHV infection. To this end, studies outlined in this research proposal are designed to evaluate the contributions of the T cell
chemoattractant chemokine IP10 (interferon inducible protein 10 kDa) in the pathogenesis of JHMV-induced demyelination. This is padicularly relevant as recent studies have implicated IP-10 as potentially important in contributing to demye!ination in MS patients by attracting T cells into the CNS. in support of this, repots from this laboratory indicate that IP-10 produced by astrocytes contributes to demyelination in JHMV-infected mice by attracting predominantly CD4+ T cells into the CNS of persistently infected mice. Specifically, antibody-mediated neutralization of IP-10 results in reduced neurologic disease, diminished demyelination, and a marked increase in the number of remyellinated axons which correlated with reduced T cell infiltration. Studies outlined in this proposal are designed to increase our understanding of how IP-10 contributes to disease in JHMV-infected mice. Novel strategies designed to accomplish this goal include (i)
examination of the molecular mechanisms contributing to IP-10 expression following either viral infection or cytokine treatment of astrocytes and (ii) examining how anti-IP-10 regulates T cell infiltration into the CNS. Together, these studies will extend our current understanding of how IP-10 controls CNS inflammation and demyelination following viral infection.
通过慢性脱髓鞘性疾病,易感小鼠感染小鼠肝炎病毒(JHMV,阳性RNA病毒)导致急性脑脊髓炎,这与人类脱髓疾病多发性硬化症(MS)具有许多相似之处。动物会出现上升的后线瘫痪,伴随着单核细胞浸润到中枢神经系统(CNS)和髓磷脂破坏中。 因此,脱髓鞘的JMHV模型是研究有助于人类脱髓鞘疾病(例如MS)的免疫病理学机制的公认模型。 T细胞和巨噬细胞被认为是MS患者的JHMV诱导的脱髓鞘以及脱髓鞘的重要促进者。该提案的远程目标是更好地了解JMHV感染后T细胞运输和进入中枢神经系统的分子机制。 为此,本研究建议中概述的研究旨在评估T细胞的贡献
在JHMV诱导的脱髓鞘发病机理中,化学吸引剂趋化因子IP10(干扰素诱导蛋白10 kDa)。这是非常相关的,因为最近的研究暗示IP-10通过将T细胞吸引到CNS中,在MS患者中有助于MS患者的Demye!Ination可能很重要。为了支持这一点,该实验室的重新机构表明,星形胶质细胞产生的IP-10通过吸引主要是CD4+ T细胞进入持续感染小鼠的中枢性,从而有助于JHMV感染小鼠的脱髓鞘。 具体而言,抗体介导的IP-10中和导致神经系统疾病降低,脱髓鞘减少以及与T细胞浸润减少相关的透明轴突数量显着增加。该提案中概述的研究旨在提高我们对IP-10对JHMV感染小鼠疾病的贡献的理解。旨在实现此目标的新型策略包括(i)
检查病毒感染或星形胶质细胞的细胞因子治疗后导致IP-10表达的分子机制,以及(ii)检查抗IP-10如何调节T细胞浸润到CNS中。总之,这些研究将扩展我们对IP-10如何控制病毒感染后CNS炎症和脱髓鞘的理解。
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)
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数据更新时间:2024-06-01
Thomas E Lane的其他基金
FASEB's "The Translational Neuroimmunology Conference: From Mechanisms to Therapeutics."
FASEB 的“转化神经免疫学会议:从机制到治疗学”。
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Chemokines and Viral-Induced Neurologic Disease
趋化因子和病毒引起的神经系统疾病
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Human neural precursor cell-mediated therapy in a viral model of demyelination
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- 财政年份:2020
- 资助金额:$ 18.27万$ 18.27万
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Human neural precursor cell-mediated therapy in a viral model of demyelination
脱髓鞘病毒模型中的人神经前体细胞介导的治疗
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- 财政年份:2015
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Viral-induced demyelination and neural stem cell-mediated remyelination
病毒诱导的脱髓鞘和神经干细胞介导的髓鞘再生
- 批准号:88859248885924
- 财政年份:2011
- 资助金额:$ 18.27万$ 18.27万
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Viral-induced demyelination and neural stem cell-mediated remyelination
病毒诱导的脱髓鞘和神经干细胞介导的髓鞘再生
- 批准号:87994818799481
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Viral-induced demyelination and neural stem cell-mediated remyelination
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Viral-induced demyelination and neural stem cell-mediated remyelination
病毒诱导的脱髓鞘和神经干细胞介导的髓鞘再生
- 批准号:84904638490463
- 财政年份:2011
- 资助金额:$ 18.27万$ 18.27万
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Viral-induced demyelination and neural stem cell-mediated remyelination
病毒诱导的脱髓鞘和神经干细胞介导的髓鞘再生
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- 资助金额:$ 18.27万$ 18.27万
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