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。

• 批准号: 22390200
• 负责人: MORIMOTO Chikao
• 金额: $ 11.98万
• 依托单位: Juntendo University (2012)The University of Tokyo (2010-2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390200/
• 关键词: CD26; DPPIV 酵素; CD28; CD8T 細胞; グランザイム B; xeno-GVHD; ヒト化 CD26 抗体; IL-10; CD26分子; 共刺激; 自己免疫疾患; ヒト免疫系; CD8T細胞; GVHD; CD28分子; サイトカイン産生; グランザイムB; 細胞障害作用; CD26/DPPIV; ヒト化CD26抗体; Granzyme B; 糖尿病; Fas Ligand

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

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: Biochemical and biophysical research communications
• 影响因子: 3.1
• 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

• DOI: 10.1016/j.bbrc.2012.02.054
• 发表时间: 2012-03-16
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Yamazaki, Hiroto;Naito, Motohiko;Morimoto, Chikao
• 通讯作者: Morimoto, Chikao

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: Diabetes
• 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

• 发表时间: 2011
• 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: BMC cancer
• 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