Basic research of defining the function of CD26 on human immune system and its clinical application for autoimmune diseases.

CD26对人体免疫系统功能的基础研究及其在自身免疫性疾病中的临床应用。

基本信息

项目摘要

CD26 is a 110-KDa surface glycoprotein with DPPIV enzyme activity that has many biological functions. We showed that CD26 costimulation induced IL -10 production and CTLA-4 expression in CD4 T cells compared to CD28 costimulation suggesting that CD26 coslimulation has a negative activation pathway. We also showed that CD26 (high) CD8 T cells belong to the early effector memory T-cell subset and that CD26 mediated co-stimulation of CD8+T cells exerts a cytotoxic effect preferentially via gramzyme B, TNF-α and Fas-ligand compared to that obtained through CD28-mediated costimulation. Moreover, we showed that CD26+T cells play an important role in GVHD mediated by human lymphocytes, and that anti-CD26mAb is an effective treatment for GVHD in hu-PBL-NOG mouse model. In addition we found that genetical or pharmacological inhibition of CD26/DPPIV enhances endothelial growth both in vitro and in vivo, suggesting that DPPIV inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications. Our results strongly suggest that CD26/DPPIV is an appropriate therapeutic target for the treatment of selected immune disorders.
CD 26是一种具有DPPIV酶活性的110-KDa表面糖蛋白,具有多种生物学功能。我们发现,与CD 28共刺激相比,CD 26共刺激诱导CD 4 T细胞中IL-10的产生和CTLA-4的表达,表明CD 26共刺激具有负活化途径。我们还发现,CD 26(高)CD 8 T细胞属于早期效应记忆T细胞亚群,并且与通过CD 28介导的共刺激获得的细胞毒性效应相比,CD 26介导的CD 8 +T细胞的共刺激优先通过gramzyme B、TNF-α和Fas-配体发挥细胞毒性效应。此外,我们发现,CD 26 +T细胞在人淋巴细胞介导的GVHD中起重要作用,并且抗CD 26 mAb是hu-PBL-NOG小鼠模型中GVHD的有效治疗。此外,我们发现,在体外和体内,CD 26/DPPIV的遗传或药理学抑制增强内皮生长,这表明DPPIV抑制在内皮生长中起着关键作用,并可能在糖尿病血管并发症后局部循环的恢复中起着潜在的作用。我们的研究结果强烈表明,CD 26/DPPIV是一个合适的治疗目标,用于治疗选定的免疫疾病。

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)
Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines.
  • DOI:
    10.1016/j.bbrc.2010.08.112
  • 发表时间:
    2010-10
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Wataru Takasawa;K. Ohnuma;R. Hatano;Y. Endo;N. Dang;C. Morimoto
  • 通讯作者:
    Wataru Takasawa;K. Ohnuma;R. Hatano;Y. Endo;N. Dang;C. Morimoto
Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells
Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice.
  • DOI:
    10.2337/db10-1338
  • 发表时间:
    2011-04
  • 期刊:
  • 影响因子:
    7.7
  • 作者:
    Shirakawa J;Fujii H;Ohnuma K;Sato K;Ito Y;Kaji M;Sakamoto E;Koganei M;Sasaki H;Nagashima Y;Amo K;Aoki K;Morimoto C;Takeda E;Terauchi Y
  • 通讯作者:
    Terauchi Y
Advances in Clinical Chemistory
临床化学进展
  • DOI:
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ohnuma K;Hosono O;Dang NH;Morimoto C
  • 通讯作者:
    Morimoto C
Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines.
  • DOI:
    10.1186/1471-2407-11-51
  • 发表时间:
    2011-02-01
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Abe M;Havre PA;Urasaki Y;Ohnuma K;Morimoto C;Dang LH;Dang NH
  • 通讯作者:
    Dang NH
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MORIMOTO Chikao其他文献

MORIMOTO Chikao的其他文献

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{{ truncateString('MORIMOTO Chikao', 18)}}的其他基金

Association of deubiquitin ligase and cell surface molecules regulates the pathophysiology of malignant pleural mesothelioma
去泛素连接酶和细胞表面分子的关联调节恶性胸膜间皮瘤的病理生理学
  • 批准号:
    24659401
  • 财政年份:
    2012
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
To determine the epigenetic regulatory mechanism of cancer stem cells by cell surface molecules.
通过细胞表面分子确定癌症干细胞的表观遗传调控机制。
  • 批准号:
    22650223
  • 财政年份:
    2010
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Basic Approach for the Development of Molecular Target Therapy for Autoimmune Diseases and Immune-Mediated Disorders.
开发自身免疫性疾病和免疫介导疾病分子靶向治疗的基本方法。
  • 批准号:
    17109011
  • 财政年份:
    2005
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (S)
Basic study of molecular target therapy for autoimmune diseases and immune deficiency diseases based on CD26
基于CD26的自身免疫性疾病及免疫缺陷病分子靶向治疗基础研究
  • 批准号:
    15209033
  • 财政年份:
    2003
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
The development of specific immune regulatory drugs utilizing the structure and function of CD26
利用CD26的结构和功能开发特异性免疫调节药物
  • 批准号:
    13557039
  • 财政年份:
    2001
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of the function of lymphocyte adhesion molecules and its clinical significances in autoimmune diseases
淋巴细胞粘附分子在自身免疫性疾病中的功能分析及其临床意义
  • 批准号:
    13470107
  • 财政年份:
    2001
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of CD29/VLA integrin in T cell immune regulation and its clinical significance
CD29/VLA整合素在T细胞免疫调节中的作用分析及其临床意义
  • 批准号:
    11307009
  • 财政年份:
    1999
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A).
Structure and function of memory T cell marker CD26
记忆T细胞标志物CD26的结构和功能
  • 批准号:
    11694248
  • 财政年份:
    1999
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Development of specific imuune regulatoly drugs by the cell surface molecules.
利用细胞表面分子开发特异性免疫调节药物。
  • 批准号:
    10557049
  • 财政年份:
    1998
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of CD26 mediated signal transduction mechanism.
CD26介导的信号转导机制分析。
  • 批准号:
    09044266
  • 财政年份:
    1997
  • 资助金额:
    $ 11.98万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
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