Establishment of transgenic mice that recognize bacteria specific antigen and develop spontaneous colitis under specific pathogen free condition.

建立识别细菌特异性抗原并在无特定病原体条件下产生自发性结肠炎的转基因小鼠。

• 批准号: 15590627
• 负责人: KANAI Takanori
• 金额: $ 2.24万
• 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 (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590627/
• 关键词: inflammatory bowel diseases; murine model; Antigen-specific; Crohn's disease; Ulcerative colitis; Probiotics; Cell transfer; Transgenic mice; 調節性T細胞; 慢性大腸炎; 調節製T細胞; 腸管粘膜免疫; 単クローン; 慢性大腸炎モデル; 自然免疫; 腸内細菌; 自己免疫疾患

In this study, we clarified that intestinal bacteria flora is essential for the development of chronic colitis using murine model of chronic colitis. We in general used adoptive transfer model that normal CD4+CD45RBhigh T cells from spleens are transferred into SCID mice. This model has the strong advadvantages that we can exactly evaluate the pathogenic T cells in clonal level.We are now under investigation to establish bacteria-specidfic antigen recognizing TCR transgenic mouse after the isolation of TCRab genes. Using this model, we believe that we can brake through to understand the exact mechanism of action in terms of antigen-specific analysis. Furthermore, we will find out a new strategy using probiotics for the treatment of inflammatory bowel diseases.

在这项研究中，我们阐明了肠道细菌植物群是必不可少的发展，慢性结肠炎小鼠模型的慢性结肠炎。我们通常采用过继转移模型，将来自脾脏的正常CD4+CD45RBhigh T细胞转移到SCID小鼠中。该模型的优点是可以在克隆水平上准确地评价致病性T细胞，我们正在研究在分离TCRab基因的基础上建立细菌特异性抗原识别TCR转基因小鼠。使用这个模型，我们相信我们可以通过抗原特异性分析来理解确切的作用机制。此外，我们将发现一种新的策略，使用益生菌治疗炎症性肠病。

项目成果

Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine

• DOI: 10.1053/j.gastro.2005.03.085
• 发表时间: 2005-06-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Matsumoto, T;Okamoto, R;Watanabe, M
• 通讯作者: Watanabe, M

Human intestinal epithelia-derived IL-18 is a potent prolifrerative factor for intraepithelial lymphocytes synergistically with IL-2, IL-7 and IL-15.

人肠上皮来源的 IL-18 是上皮内淋巴细胞的有效增殖因子，与 IL-2、IL-7 和 IL-15 具有协同作用。

• 发表时间: 2004
• 期刊: Clin Exp Immunol 136
• 作者: Okazawa A;Kanai T;Nakamaru T;Sato T;Inoue N;Ogata H;Iwao Y;Ikeda M;Kawamura T;Makita S;Uraushihara K;Okamoto R;Yamazaki M;Kurimoto M;Ishii H;Watanabe M;Hibi T.
• 通讯作者: Hibi T.

Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of IL-7 in human intestinal epithelial cells.

干扰素调节因子 1 (IRF-1) 和 IRF-2 明显上调人肠上皮细胞中基因表达和 IL-7 的产生。

• 发表时间: 2004
• 期刊: Mol Cell Biol 24
• 作者: Oshima S;Kanai T;et al.
• 通讯作者: et al.

T-bet up-regulation and subsequent interleukin 12 stimulation are essential for the induction of Th1 mediated immunopathology in Crohn's disease.

T-bet 上调和随后的白细胞介素 12 刺激对于克罗恩病中 Th1 介导的免疫病理学的诱导至关重要。

• 发表时间: 2004
• 期刊: Gut 53
• 作者: Matsuoka K;Inoue N;Sato T;Okamoto S;Hisamatsu T;Kishi Y;Sakuraba A;Hitotsumatsu O;Fukushima T;Kanai T;Watanabe M;Ishii H;Hibi T
• 通讯作者: Hibi T

Totsuka T, Kanai T, et al.: "Ameliorating Effect of Anti-Inducible Costimulator Monoclonal Antibody in a Murine Model of Chronic Colitis"Gastroenterology. 124. 410-421 (2003)

Totsuka T、Kanai T 等人：“抗诱导共刺激单克隆抗体在慢性结肠炎小鼠模型中的改善作用”胃肠病学。