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Development of the new immunological tolerance induction which uses Notch ligands in islet transplantation

在胰岛移植中使用Notch配体开发新的免疫耐受诱导

基本信息

批准号：
18591414
负责人：
SOEJIMA Yuji
金额：
$ 2.43万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591414/
关键词：
Notch Japped 1 Deltal immunosupression Jaeeed1

项目摘要

It has been shown that the Delta family, which is one of Notch ligand family, control the immune response in positive direction. But, as for the function in immune response of the Jagged family, which is another Notch ligand family, the part which still does not become clear is a lot. This time we have focused on the function and the especially immune response control action in the immune response of Jagged 1. With the result of in vitro; in the Delta1 revelation dendritic cell, it could recognize the reinforcement of cell proliferation, but it had decreased by comparison with the contrast group in the Jagged I revelation dendritic cell proliferation (reported in the 106th annual congress of Japan Surgical Society). From this research, the possibility was shown that Jagged 1 has controlled immune response in negative direction, and through the T lymphocyte the donor unique low reactivity can be introduced in transplantation immunity.With the result of in vivo, in the A20 cell which introduces Jagged2, the tumor area reduced by comparison with control. In addition, the secretion of IFN- and Granzyme B increased by introducing the Jagged2 gene, could recognize the activation of NK cell. (Proc Natl Acad Sci USA (2008) in press)From these results, it was recognized that Notch ligands could participate not only transplantation immunity but also tumor immunity, and was suggested the possibility of the controlling the rejection in transplantation by Notch ligands and the development of the new remedy for the tumor.

研究表明，Notch配体家族中的Delta家族正向调控免疫应答。但是，关于另一个Notch配体家族Jagged家族在免疫应答中的作用，还有很多不清楚的地方。本文重点介绍了Jagged 1在免疫应答中的功能，特别是免疫应答控制作用。体外实验结果；在Delta1启示树突状细胞中，它可以识别细胞增殖的强化，但在Jagged I启示树突状细胞增殖中，它比对照组有所下降（报道于第106届日本外科学会年会上）。本研究可能表明Jagged 1具有负向控制免疫应答的功能，通过T淋巴细胞将供体特有的低反应性引入移植免疫。体内实验结果表明，在引入Jagged2的A20细胞中，肿瘤面积较对照组缩小。此外，引入Jagged2基因后，IFN-和颗粒酶B的分泌增加，可以识别NK细胞的活化。（Proc Natl Acad Sci USA (2008) in press）这些结果认识到Notch配体不仅可以参与移植免疫，还可以参与肿瘤免疫，并提出了Notch配体控制移植排斥反应和开发肿瘤新疗法的可能性。