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)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Thomas E Lane其他文献
Thomas E Lane的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Thomas E Lane', 18)}}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”。
- 批准号:
10065269 - 财政年份:2020
- 资助金额:
$ 18.27万 - 项目类别:
Defining mechanisms of disease and repair in a viral model of multiple sclerosis
定义多发性硬化症病毒模型中的疾病和修复机制
- 批准号:
10640816 - 财政年份:2020
- 资助金额:
$ 18.27万 - 项目类别:
Chemokines and Viral-Induced Neurologic Disease
趋化因子和病毒引起的神经系统疾病
- 批准号:
10090528 - 财政年份:2020
- 资助金额:
$ 18.27万 - 项目类别:
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
- 批准号:
10076583 - 财政年份:2020
- 资助金额:
$ 18.27万 - 项目类别:
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
- 批准号:
8874463 - 财政年份:2015
- 资助金额:
$ 18.27万 - 项目类别:
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:
8885924 - 财政年份:2011
- 资助金额:
$ 18.27万 - 项目类别:
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:
8799481 - 财政年份:2011
- 资助金额:
$ 18.27万 - 项目类别:
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:
8291218 - 财政年份:2011
- 资助金额:
$ 18.27万 - 项目类别:
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:
8490463 - 财政年份:2011
- 资助金额:
$ 18.27万 - 项目类别:
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:
8152289 - 财政年份:2011
- 资助金额:
$ 18.27万 - 项目类别:
相似国自然基金
IL-15调控CD8+CD57+T淋巴细胞抗肿瘤免疫应答的作用和机制研究
- 批准号:82303170
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
GBP4调控T淋巴细胞所致早发冠心病的机制研究
- 批准号:82370336
- 批准年份:2023
- 资助金额:47 万元
- 项目类别:面上项目
CD40/CD40L通路激活CD8+毒性T淋巴细胞调控TED眼眶组织重塑的机制研究
- 批准号:82371105
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
成人免疫性血小板减少症(ITP)中血小板因子4(PF4)通过调节CD4+T淋巴细胞糖酵解水平影响Th17/Treg平衡的病理机制研究
- 批准号:82370133
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
基于神经重编程探究电针围刺促进乳腺癌CD8+T淋巴细胞募集的抗肿瘤机制
- 批准号:82305396
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Molecularly targeted, multidisciplinary glioma vaccine approaches
分子靶向、多学科神经胶质瘤疫苗方法
- 批准号:
8377644 - 财政年份:2002
- 资助金额:
$ 18.27万 - 项目类别:
Molecularly targeted, multidisciplinary glioma vaccine approaches
分子靶向、多学科神经胶质瘤疫苗方法
- 批准号:
7408984 - 财政年份:2002
- 资助金额:
$ 18.27万 - 项目类别:
Molecularly targeted, multidisciplinary glioma vaccine approaches
分子靶向、多学科神经胶质瘤疫苗方法
- 批准号:
8074415 - 财政年份:2002
- 资助金额:
$ 18.27万 - 项目类别:
Molecularly targeted, multidisciplinary glioma vaccine approaches
分子靶向、多学科神经胶质瘤疫苗方法
- 批准号:
8232995 - 财政年份:2002
- 资助金额:
$ 18.27万 - 项目类别:
Molecularly targeted, multidisciplinary glioma vaccine approaches
分子靶向、多学科神经胶质瘤疫苗方法
- 批准号:
7903408 - 财政年份:2002
- 资助金额:
$ 18.27万 - 项目类别: