A novel pathway regulating cytokine production and asthma development
调节细胞因子产生和哮喘发展的新途径
基本信息
- 批准号:7356481
- 负责人:
- 金额:$ 23.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-15 至 2011-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcademiaAllergicAlzheimer&aposs DiseaseAmyloidAmyloid beta-Protein PrecursorAsthmaAttenuatedCD4 Positive T LymphocytesCell Differentiation processCell physiologyCell surfaceDevelopmentDiseaseDrug Delivery SystemsDrug DesignExhibitsExtracellular MatrixExtracellular Matrix ProteinsHelper-Inducer T-LymphocyteImmune responseIndustryInvestigationLDL-Receptor Related Protein 1LeadLigandsMediatingMusNeuronsPathogenesisPathway interactionsPharmaceutical PreparationsPlayProductionProtein PrecursorsReceptor-CD3 Complex, Antigen, T-CellRegulationResearchRoleSignal PathwaySignal TransductionT-LymphocyteTestingWorkcytokineinsightnovelpathogenreceptor
项目摘要
DESCRIPTION: Cytokines produced by CD4+ T lymphocytes play essential roles in host adaptive immune responses and are involved in the development of allergic diseases including asthma. Our understanding of the pathways regulating cytokine production in CD4+ T lymphocytes remains incomplete. We have identified a novel pathway regulating cytokine production in CD4+ T cells using molecules that are thought to be primarily involved in neuronal cell function and pathogenesis of Alzheimer's disease. We show that CD4+ T cells lacking the extracellular matrix (ECM) protein F-spondin or its receptor apoE receptor 2 (ApoER2) exhibit defective cytokine production, and asthma development is attenuated in mice lacking F-spondin. Our overall hypothesis is that F-spondin and its receptors ApoER2 and amyloid-2 precursor protein (APP) constitute a novel ligand-receptor pairs whose interaction on the CD4+ T cell surface provides a critical signal to initiate cytokine production. To test this hypothesis, we propose two specific aims: 1. To establish the mechanisms by which F-spondin regulates CD4+ T lymphocyte cytokine production. 2. To examine the signaling pathway mediated by ApoER2 and APP in CD4+ T lymphocyte cytokine production. Results from these studies will not only provide important mechanistic insights into the regulation of CD4+ T lymphocyte cytokine production and asthma development, but also may lead to discoveries of novel drug targets for asthma treatment. Given the current effort by industry and academia to develop Alzheimer's disease treatments, our proposed research may be able to redirect the drugs developed for Alzheimer's disease into asthma treatment. Project Narrative
Cytokines produced by CD4+ T lymphocytes are involved in the development of allergic diseases including asthma. Our understanding of the pathways regulating cytokine production and asthma development remains incomplete. Investigation of the pathways regulating cytokine production and asthma development will lead to new discoveries that will help drug designs for asthma treatment. Our recent work has identified a novel pathway regulating cytokine production in CD4+ T cells and asthma development in mice by molecules that are thought to be primarily involved in neuronal cell function and pathogenesis of Alzheimer's disease. Given the current effort in the development of Alzheimer's disease treatment by industry and academia, our proposed research may be able to redirect the drugs developed for Alzheimer's disease into asthma treatment.
描述:CD4+ T 淋巴细胞产生的细胞因子在宿主适应性免疫反应中发挥重要作用,并参与包括哮喘在内的过敏性疾病的发展。我们对调节 CD4+ T 淋巴细胞细胞因子产生的途径的了解仍然不完整。我们使用被认为主要参与神经元细胞功能和阿尔茨海默氏病发病机制的分子,确定了调节 CD4+ T 细胞中细胞因子产生的新途径。我们发现,缺乏细胞外基质 (ECM) 蛋白 F-spondin 或其受体 apoE 受体 2 (ApoER2) 的 CD4+ T 细胞表现出细胞因子产生缺陷,并且缺乏 F-spondin 的小鼠中哮喘的发展减弱。我们的总体假设是,F-spondin 及其受体 ApoER2 和淀粉样蛋白 2 前体蛋白 (APP) 构成了一种新型配体-受体对,其在 CD4+ T 细胞表面上的相互作用提供了启动细胞因子产生的关键信号。为了检验这一假设,我们提出了两个具体目标: 1. 建立 F-spondin 调节 CD4+ T 淋巴细胞细胞因子产生的机制。 2. 检测ApoER2和APP在CD4+ T淋巴细胞细胞因子产生中介导的信号通路。这些研究的结果不仅将为 CD4+ T 淋巴细胞细胞因子产生和哮喘发展的调节提供重要的机制见解,而且还可能导致哮喘治疗新药物靶点的发现。鉴于目前工业界和学术界正在努力开发阿尔茨海默病治疗方法,我们提出的研究可能能够将针对阿尔茨海默病开发的药物重新用于哮喘治疗。项目叙述
CD4+ T 淋巴细胞产生的细胞因子参与包括哮喘在内的过敏性疾病的发生。我们对调节细胞因子产生和哮喘发展的途径的理解仍然不完整。对调节细胞因子产生和哮喘发展的途径的研究将带来新的发现,有助于哮喘治疗的药物设计。我们最近的工作发现了一种新的途径,通过被认为主要参与神经元细胞功能和阿尔茨海默氏病发病机制的分子来调节 CD4+ T 细胞中细胞因子的产生和小鼠哮喘的发展。鉴于目前工业界和学术界在开发阿尔茨海默病治疗方面所做的努力,我们提出的研究可能能够将针对阿尔茨海默病开发的药物重新用于哮喘治疗。
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 }}
You-Wen He其他文献
You-Wen He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('You-Wen He', 18)}}的其他基金
The impact of genetic diversity among Akkermansia strains on the effectivenes of immune checkpoint inhibitors in cancer immunotherapies
阿克曼氏菌菌株遗传多样性对癌症免疫治疗中免疫检查点抑制剂有效性的影响
- 批准号:
10115682 - 财政年份:2020
- 资助金额:
$ 23.4万 - 项目类别:
A novel pathway regulating cytokine production and asthma development
调节细胞因子产生和哮喘发展的新途径
- 批准号:
7843494 - 财政年份:2009
- 资助金额:
$ 23.4万 - 项目类别:
BcI-2 family in T lymphocyte homeostasis
Bcl-2 家族在 T 淋巴细胞稳态中的作用
- 批准号:
8389558 - 财政年份:2008
- 资助金额:
$ 23.4万 - 项目类别:
BcI-2 family in T lymphocyte homeostasis
Bcl-2 家族在 T 淋巴细胞稳态中的作用
- 批准号:
7580414 - 财政年份:2008
- 资助金额:
$ 23.4万 - 项目类别:
Function of thymic epithelial cells in T lymphocyte maturation
胸腺上皮细胞在T淋巴细胞成熟中的功能
- 批准号:
7686243 - 财政年份:2008
- 资助金额:
$ 23.4万 - 项目类别:
相似海外基金
Elucidation of the mechanisms of clothing-induced allergic symptoms and quantification of itching
阐明衣服引起的过敏症状的机制和瘙痒的量化
- 批准号:
23H00914 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mechanism of Retinal Choroidal Inflammation in Chronic Severe Allergic Conjunctivitis
慢性重症过敏性结膜炎视网膜脉络膜炎症机制
- 批准号:
23K15918 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Lung resident Treg suppression of Th2 resident memory T cells in allergic asthma
过敏性哮喘中肺常驻 Treg 对 Th2 常驻记忆 T 细胞的抑制
- 批准号:
10664599 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Gut Microbial Factors in Farming Lifestyle and Allergic Sensitization
农业生活方式和过敏致敏中的肠道微生物因素
- 批准号:
10633368 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Role of Skin Barrier and Immune Alterations in Allergic Sensitization
皮肤屏障和免疫改变在过敏性致敏中的作用
- 批准号:
10633370 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Elucidation of the mechanisms by which paired immune receptors recognize their ligands and development of treatments for allergic and inflammatory diseases
阐明配对免疫受体识别其配体的机制并开发过敏性和炎症性疾病的治疗方法
- 批准号:
23H02946 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Genetic analysis of the pathogenesis of atopic dermatitis focusing on the allergic sensitivity of NC mice.
以NC小鼠过敏敏感性为重点的特应性皮炎发病机制的遗传分析。
- 批准号:
23K05600 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Relationship between changes in intestinal microflora and anti-allergic effects caused by ingestion of koji-fermented soybeans
摄入曲发酵大豆引起的肠道菌群变化与抗过敏作用的关系
- 批准号:
23K02043 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of a highly sensitive and specific POCT testing asthma triggering allergic IgE
开发高度敏感和特异的 POCT 测试哮喘触发过敏性 IgE
- 批准号:
10600767 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
The effects of wildfire exposure on maternal allergic asthma and consequences on neurobiology
野火暴露对母亲过敏性哮喘的影响及其对神经生物学的影响
- 批准号:
10727122 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:














{{item.name}}会员




