Studies on the pathogenesis of Graves' disease and new treatment using our recently established mouse model.

使用我们最近建立的小鼠模型研究格雷夫斯病的发病机制和新的治疗方法。

基本信息

  • 批准号:
    17590965
  • 负责人:
  • 金额:
    $ 2.18万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

1. Suppression of disease development by CD4^+CD25^+ regulatory T cells (Treg) : Depletion of Treg by anti-CD25 antibody induced Graves' hyperthyroidism in 30 % of resistant C57BL/6 mice, and increased serum T_4 levels by 200 % in susceptible BALB/c mice. This effect was attributed to decreased stimulatory antibody titers and increased blocking antibody titers. Furthermore, in transfer experiments to naive wt mice, splenocytes from Graves' mice induced little anti-TSHR antibody, but CD25-depleted splenocytes did low but significant levels of antibody.2. Suppression of disease development by regulatory cytokines : adenovirus expressing IL-10 or TGF-beta (both are regulatory cytokines) were constructed, and administered to mice together with adenovirus coding the TSHR (Ad-TSHR). Only Ad-IL-10 significantly inhibited hyperthyroidism.3. Suppression of disease development by apoptosis-inducing Fas ligand (FasL) : Adenovirus expressing FasL was constructed, and infected into dendritic cells (DCs) derived from bone-marrow cells by using GMCSF and IL-4 together with Ad-TSHR. These DCs inhibited anti-TSHR immune response and development of Graves' disease induced by intramuscular injection of Ad-TSHR.4. TSHR-specific T cell lines are now being established by the TSHR protein and three : peptides which induced IFNgamma release in recall assay. Abilities of individual clones to produce cytokine(s) and to induce hyperthyroidism as well as amino acid sequences of T cell receptors will be studied.
1.CD_4~+CD25~+调节性T细胞(Treg)抑制疾病的发生:抗CD25抗体去除Treg后,30%耐药的C57BL/6小鼠出现Graves‘甲亢,易感BALB/c小鼠血清T_4水平升高200%。这种效果归因于刺激性抗体效价的降低和阻断抗体效价的增加。此外,在对幼小鼠的移植实验中,来自Graves‘s小鼠的脾细胞诱导了少量的抗TSHR抗体,但CD25耗竭的脾细胞产生了低水平但显著的抗体水平。调节性细胞因子抑制疾病进展:构建表达IL-10或TGF-β的腺病毒(两者均为调节性细胞因子),并与编码TSHR的腺病毒(Ad-TSHR)一起接种于小鼠。仅Ad-IL-10能显著抑制甲亢。通过凋亡诱导Fas配体(FasL)抑制疾病进展:构建表达FasL的腺病毒,并用GMCSF和IL-4联合Ad-TSHR感染骨髓来源的树突状细胞(DC)。这些树突状细胞抑制肌肉注射Ad-TSHR诱导的抗TSHR免疫应答和Graves病的发生。TSHR特异的T细胞系目前正在由TSHR蛋白和三种多肽建立:在Recall实验中诱导IFNGamma释放的多肽。将研究单个克隆产生细胞因子(S)和诱导甲状腺功能亢进的能力以及T细胞受体的氨基酸序列。

项目成果

期刊论文数量(26)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Adenovirus-mediated gene delivery of interleukin-10, but not transforming growth factor beta, ameliorates Graves' hyperthyroidism in BALB/c mice.
腺病毒介导的白细胞介素 10(但不转化生长因子 β)基因传递可改善 BALB/c 小鼠的格雷夫斯甲状腺功能亢进症。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Saitoh O;Mizutori Y;Takamura N;Kita A;Kuwahara H;Yamasaki H;Nagayama Y.
  • 通讯作者:
    Nagayama Y.
BRAFV600E promotes invasiveness of thyroid cancer cells through NF-kB activation
BRAFV600E通过NF-kB激活促进甲状腺癌细胞的侵袭
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    I.Palona;et al.
  • 通讯作者:
    et al.
Animal model of Graves' disease.
格雷夫斯病的动物模型。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hayashi T;Nakao K;Nagayama Y;Saitoh O;Ichikawa T;Ishikawa H;Hamasaki K;Eguchi K;Ishii N.;柴田洋孝;柴田洋孝;Nagayama Y.
  • 通讯作者:
    Nagayama Y.
Adenovirus coding the thyrotropin receptor A subunit improves the efficacy of dendritic cell-based mouse model of Graves' hyperthyroidism.
编码促甲状腺素受体 A 亚基的腺病毒可提高基于树突状细胞的格雷夫斯甲状腺功能亢进症小鼠模型的疗效。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Shiro;Yosioka.;Kenichi Yokota;Yoshimoto K et al.;Mizutori Y
  • 通讯作者:
    Mizutori Y
Regulation of Graves' hyperthyroidism with naturally occurring CD4+CD25+ regulatory T cells in a mouse model
  • DOI:
    10.1210/en.2005-1024
  • 发表时间:
    2006-05-01
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    Saitoh, O;Nagayama, Y
  • 通讯作者:
    Nagayama, Y
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NAGAYAMA Yuji其他文献

NAGAYAMA Yuji的其他文献

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{{ truncateString('NAGAYAMA Yuji', 18)}}的其他基金

Studies on thyorid cancer pathogenesis using mouse models
利用小鼠模型研究甲状腺癌发病机制
  • 批准号:
    19K09028
  • 财政年份:
    2019
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on thyroid autoimmunity: anti-mouse TSH receptor immune response and central tolerance in mice
甲状腺自身免疫研究:小鼠抗小鼠TSH受体免疫反应和中枢耐受
  • 批准号:
    15K09437
  • 财政年份:
    2015
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on thyroid autoimmunity: anti-TSHR immune response and tolerance in mice
甲状腺自身免疫研究:小鼠抗 TSHR 免疫反应和耐受性
  • 批准号:
    24591368
  • 财政年份:
    2012
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on the pathogenesis of autoimmune thyroid diseases : using genetically-engineered mice
自身免疫性甲状腺疾病发病机制的研究:利用基因工程小鼠
  • 批准号:
    20591099
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on the poathogenesis of Graves' disease and new treatment using our recently established mouse model.
使用我们最近建立的小鼠模型研究格雷夫斯病的发病机制和新的治疗方法。
  • 批准号:
    14571069
  • 财政年份:
    2002
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Evaluation of the therapeutic effect of replication-competent adenovirus on thyroid carcinomas
具有复制能力的腺病毒对甲状腺癌的治疗效果评价
  • 批准号:
    12671090
  • 财政年份:
    2000
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on structure-function of the thyrotropin receptor : molecular biological analysis of post-translational modifications
促甲状腺素受体的结构功能研究:翻译后修饰的分子生物学分析
  • 批准号:
    09671064
  • 财政年份:
    1997
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Thyrotropin Receptor, Thyrotropin and Mechanisms of Bone Loss
促甲状腺素受体、促甲状腺素与骨丢失机制
  • 批准号:
    10182095
  • 财政年份:
    2017
  • 资助金额:
    $ 2.18万
  • 项目类别:
Thyrotropin Receptor, Thyrotropin and Mechanisms of Bone Loss
促甲状腺素受体、促甲状腺素与骨丢失机制
  • 批准号:
    9317142
  • 财政年份:
    2017
  • 资助金额:
    $ 2.18万
  • 项目类别:
Thyrotropin Receptor, Thyrotropin and Mechanisms of Bone Loss
促甲状腺素受体、促甲状腺素与骨丢失机制
  • 批准号:
    9906208
  • 财政年份:
    2017
  • 资助金额:
    $ 2.18万
  • 项目类别:
New TSHR Antagonists as a potential approach to bridge the therapeutic gap of Graves' ophthalmopathy as follow up to' Modulators fort he Thyrotropin receptor: Molekular mechansims allosteric binding and mode of action of small molecules'
新的 TSHR 拮抗剂作为弥补格雷夫斯眼病治疗差距的潜在方法,作为“促甲状腺激素受体调节剂:分子机制模拟变构结合和小分子作用模式”的后续行动
  • 批准号:
    131071061
  • 财政年份:
    2009
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Research Grants
Thyrotropin Receptor Auto Antibodies in Graves' Ophthalmopathy
格雷夫斯眼病中的促甲状腺素受体自身抗体
  • 批准号:
    7624632
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
Thyrotropin Receptor Autoantibodies in Graves' Ophthalmopathy
格雷夫斯眼病中的促甲状腺素受体自身抗体
  • 批准号:
    8539865
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
Thyrotropin Receptor Auto Antibodies in Graves' Ophthalmopathy
格雷夫斯眼病中的促甲状腺素受体自身抗体
  • 批准号:
    8062810
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
Thyrotropin Receptor Auto Antibodies in Graves' Ophthalmopathy
格雷夫斯眼病中的促甲状腺素受体自身抗体
  • 批准号:
    7242916
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
REGULATION OF EXPRESION OF THE HUMAN THYROTROPIN RECEPTOR AND FUNCTIONAL ANALYSIS OF THE PROMOTER OF THE GENE
人促甲状腺激素受体的表达调控及基因启动子的功能分析
  • 批准号:
    10671042
  • 财政年份:
    1998
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on mechanisms of induction of anti-thyrotropin receptor antibodies in murine experimental Graves'disease.
小鼠实验性格雷夫斯病抗促甲状腺素受体抗体诱导机制研究。
  • 批准号:
    09670468
  • 财政年份:
    1997
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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