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
• 负责人: MORIMOTO Chikao
• 金额: $ 71.72万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17109011/
• 关键词: 膠原病; リウマチ学; 臨床免疫学; CD26; caveolin-1; 共刺激分子; DPPIV; 自己免疫疾患; CD8T細胞; Xeno-GVHD; CD28; caveolin.1; DPPIV酵素; ヒト化CD26抗体; 異種GVHDマウス; CD26陽性T細胞; TIA-1陽性T細胞; エフェクターT細胞; メモリーT細胞; CD86; 共刺激リガンド; CARMA-1; Caveolin-1; Tollip; IRAK-1

We have identified caveolin-1 as the costimulatory ligand for CD26. The 82-101th amino acid (a・a) of caveolin-1 bound to the 201-211th a・a of CD26 with the DPPIV catalytic site of 630^<th> a・a, Serine. Moreover, we found that cytoplasmic tail of CD26 interacts with CARMA-1 in T cells, resulting in the induction of costimulatory signal. After injection of human PBL into SCID mice, the symptom of xeno-GVHD has been induced and human T cells play a role in pathophysiology of x-GVHD as effectors. Treatment of these x-GVHD mice with humanized CD26 antibody resulted in improvement of the symptom of x-GVHD, suggesting that anti-CD26 treatment leads to the effective treatment of human immune-mediated diseases such as autoimmune disorders and GVHD after allo-BMT.

我们已经确定 Caveolin-1 是 CD26 的共刺激配体。 Caveolin-1的第82-101个氨基酸(a·a)与CD26的第201-211个a·a结合，DPPIV催化位点为第630个a·a，丝氨酸。此外，我们发现CD26的胞质尾部与T细胞中的CARMA-1相互作用，导致共刺激信号的诱导。 SCID小鼠注射人PBL后，会诱发xeno-GVHD症状，人T细胞作为效应器在x-GVHD的病理生理学中发挥作用。用人源化 CD26 抗体治疗这些 x-GVHD 小鼠，导致 x-GVHD 症状得到改善，表明抗 CD26 治疗可以有效治疗人类免疫介导的疾病，如自身免疫性疾病和同种异体 BMT 后的 GVHD。

项目成果

Nedd9 Protein, a Cas-L Homologue, Is Upregulated After Transient Global Ischemia in Rats: Possible Involvement of Nedd9 in the Differentiation of Neurons After Ischemia

• DOI: 10.1161/01.str.0000185672.10390.30
• 发表时间: 2005-11
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Takahiro Sasaki;S. Iwata;H. Okano;Y. Urasaki;Junichi Hamada;Hirotoshi Tanaka;N. Dang;H. Okano;C. Morimoto

Could serum antibody to poly(ADP-ribose)and/or histone Hl be marker for senile dementia of Alzheimer type?

抗聚（ADP-核糖）和/或组蛋白 H1 的血清抗体能否作为阿尔茨海默型老年痴呆的标志物？

• 发表时间: 2007
• 期刊: Ann N Y Acad Sci 1109
• 作者: Kanai Y;Akatsu H;Iizuka H;Morimoto C
• 通讯作者: Morimoto C

Stem cell properties and the side population cells as a target for interferon-alpha in adult T-cell leukemia/Imhoma

干细胞特性和侧群细胞作为成人 T 细胞白血病/Imhoma 干扰素-α 的靶标

• 发表时间: 2007
• 期刊: Biochem Biophys Res Commun 364
• 作者: Kayo H;Yamazaki H;Nishida H;Dang NH;Morimoto C
• 通讯作者: Morimoto C

Anti-CD26 monoclonal antibody-mediated GI-S arrest of human renal clear cell carcinoma Caki-2 is associated with retinoblastoma substrate dephosphorylation, cyclin-dependent kinase 2 reduction, p27(kipl)enhancement,and disruption of binding to the extrace

抗 CD26 单克隆抗体介导的人肾透明细胞癌 Caki-2 的 GI-S 阻滞与视网膜母细胞瘤底物去磷酸化、细胞周期蛋白依赖性激酶 2 减少、p27(kipl) 增强和与额外物结合的破坏有关

• 发表时间: 2006
• 期刊: Clin cancer Res. 12
• 作者: Inamoto T;Morimoto C;et al.
• 通讯作者: et al.

Regulation of p38 phosphorylation and topoisomerase llalpha expression in the B-cell lymphoma line Jiyoye by CD26/dipeptidyl peptidase IV is associated with enhanced in vitro and in vivo sensitivity to doxorubicin.

CD26/二肽基肽酶 IV 对 B 细胞淋巴瘤系 Jiyoye 中 p38 磷酸化和拓扑异构酶 llalpha 表达的调节与体外和体内对阿霉素敏感性的增强有关。

• 发表时间: 2005
• 期刊: Cancer Res. 65
• 作者: Yamochi T;Morimoto C;et al.
• 通讯作者: et al.