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Elucidation of the mechanism for regurating mucosal immune response and application for the treatment of chronic colitis and food allergy.

阐明调节粘膜免疫反应的机制及其在治疗慢性结肠炎和食物过敏中的应用。

基本信息

批准号：
13470116
负责人：
WATANABE Mamoru
金额：
$ 9.02万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

We have established a concept of intramucosal network system composed of IL-7-producing epithelial cells and IL-7R-expressing lymphoid cells, and clarified the significant roles of this network in mucosal immune regulation within the gut. In the current project, we have attempted to further elucidate the regulatory mechanisms of mucosal immune system concerning the IL-7/IL-7R network and the intestinal epithelial cell (IEC) functions. Until present, we have developed an experimental system where IL-7R-expressing cells are efficiently targeted by in vivo administration of immunotoxic anti-IL-7R antibodies that are linked to saporin. Our findings that direct immunotoxin targeting of DL-7R caused significant amelioration of chronic colitis in several model mice proposed the IL-7/IL-7R system to be a novel therapeutic target for a certain type of chronic colitis in humans. We have also investigated the physiology of BECs and have reported that bone marrow (BM)-derived cells can repopulate the epithelia of the human gastrointestinal tract. Moreover, the potentials of BM cells to transdifferentiate into lECs are shown to be important for the promotion ofregenerating process of severely damaged epithelia. Further analysis and integration of the results of our investigations would provide not only a better understanding of the mechanisms of mucosal immune regulation, but also potential therapeutic approaches directed to immune regulation and promotion of tissue repair in human diseases.

我们已经建立了由IL-7产生上皮细胞和IL-7 R表达淋巴细胞组成的粘膜内网络系统的概念，并阐明了该网络在肠道粘膜免疫调节中的重要作用。本课题旨在进一步阐明IL-7/IL-7 R网络和肠上皮细胞（IEC）功能在黏膜免疫系统中的调控机制。到目前为止，我们已经开发了一种实验系统，其中IL-7 R表达细胞通过体内施用与皂草素连接的免疫毒性抗IL-7 R抗体来有效靶向。我们的研究结果表明，直接免疫毒素靶向DL-7 R导致几种模型小鼠的慢性结肠炎的显着改善，提出IL-7/IL-7 R系统是人类某种类型慢性结肠炎的新的治疗靶点。我们还研究了BEC的生理学，并报道了骨髓（BM）来源的细胞可以重新填充人胃肠道的上皮细胞。此外，BM细胞转分化为lEC的潜力被证明对于促进严重损伤的上皮的再生过程是重要的。对我们研究结果的进一步分析和整合不仅可以更好地理解粘膜免疫调节的机制，而且还可以提供针对免疫调节和促进人类疾病组织修复的潜在治疗方法。