2012 Fiscal Year Final Research Report
Basic research of defining the function of CD26 on human immune system and its clinical application for autoimmune diseases.
| Project/Area Number |
22390200
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Juntendo University (2012)
The University of Tokyo (2010-2011) |
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Principal Investigator |
MORIMOTO Chikao 順天堂大学, 大学院・医学研究科, 客員教授 (30119028)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Satoshi 東京大学, 医科学研究所, 特任講師 (00396871)
HOSONO Osamu 東京大学, 医科学研究所, 講師 (50190210)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMADA Taketo 慶應義塾大学, 医学部, 准教授 (60230463)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 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 |
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| Research Abstract |
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.
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[Journal Article] CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma2012
Author(s)
Aoe K, Amatya VJ, Fujimoto N, Ohnuma K, Hosono O, Hiraki A, Fujii M, Yamada T, Dang NH, Takeshima Y, Inai K, Kishimoto T, Morimoto C
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Journal Title
Clin Cancer Res
Volume: 18
Pages: 1447-1456
DOI
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[Journal Article] Diet-Induced Adipose Tissue Inflammation and Liver Steatosis Are Prevented by DPP-4 Inhibition in Diabetic Mice2011
Author(s)
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
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Journal Title
Diabetes
Volume: 60
Pages: 1246-57
DOI
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