Challenges towards the generation of the dream immunosuppressant for the 21stcentury without permanent medication

开发 21 世纪理想的无需永久性药物的免疫抑制剂面临的挑战

• 批准号: 23658093
• 负责人: KAWAMOTO Seiji
• 金额: $ 2.5万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23658093/
• 关键词: 拒絶反応; 制御性 T 細胞; 免疫抑制抗体; 制御性T細胞; 国際情報交流

Immunosuppressant is essential for transplantation, but current drug has problems such as the need of permanent medication or the risk of fatal side effects. In the present study, I sought to elucidate the mode of action of immunosuppressive antibody (anti-H1 antibody) induced in a rat model of tolerogeneic liver transplantation, and demonstrate its therapeutic efficacy in vivo. Here I found that the immunosuppressive anti-H1 antibody acted directly on T cells to exert its immunosuppressive activity, and that the anti-H1 antibody suppressed T cell activation in regulatory T cell dependent- and -independent mechanisms. I also showed that the anti-H1 antibody prolonged allograft survival in a rat model of heterotopic heart transplantation.

免疫抑制剂对于移植是必不可少的，但目前的药物存在诸如需要长期用药或有致命副作用的风险等问题。在本研究中，我试图阐明免疫抑制抗体（抗h1抗体）在大鼠耐受性肝移植模型中的作用方式，并证明其在体内的治疗效果。这里我发现免疫抑制抗h1抗体直接作用于T细胞发挥其免疫抑制活性，并且抗h1抗体以调节性T细胞依赖和不依赖的机制抑制T细胞活化。我还表明，抗h1抗体延长同种异体心脏移植大鼠模型的存活时间。

项目成果

Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.

• DOI: 10.1371/journal.pone.0037202
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Nakano T;Lai CY;Goto S;Hsu LW;Kawamoto S;Ono K;Chen KD;Lin CC;Chiu KW;Wang CC;Cheng YF;Chen CL
• 通讯作者: Chen CL

A unique T cell regulatory role of anti-histone H1 autoantibody: its mode of action through regulatory T cell-dependent and -independent mechanisms

抗组蛋白 H1 自身抗体独特的 T 细胞调节作用：其通过调节 T 细胞依赖性和非依赖性机制发挥作用的模式

• 发表时间: 2013
• 作者: Takaoka Y.;Kawamoto S.;Katayama A.;Nakano T.;Yamanaka Y.;Takahashi M.;Shimada Y.;Chiang K. C.;Ohmori N.;Aki T.;Goto T.;Sato S.;Goto S.;Chen C. L.;Ono K.
• 通讯作者: Ono K.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

• DOI: 10.1016/j.bbrc.2012.12.125
• 发表时间: 2013-02-08
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Takaoka, Yuki;Kawamoto, Seiji;Ono, Kazuhisa
• 通讯作者: Ono, Kazuhisa

Autoimmunity and liver transplantation immunology

自身免疫与肝移植免疫学

• 发表时间: 2011
• 期刊: Curr. Trends Immunol
• 作者: Goto S.;Nakano T.;Hsu L. W.;Chiang K. C.;Lai C. Y.;Kawamoto S.;Ono K.;Chen K. D.;Ohmori N.;Goto T.;Sato S.;Wang C. C.;Jawan B.;Cheng F. Y.;Chen C. L.
• 通讯作者: Chen C. L.