Study of mucosal immune response in the murine model of inflammatory bowel disease -Therapeutic effect of a new immunosuppressive reagent FTY720-

炎症性肠病小鼠模型粘膜免疫反应研究-新型免疫抑制试剂FTY720的治疗效果-

• 批准号: 13671301
• 负责人: ITO Toshinori
• 金额: $ 1.98万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671301/
• 关键词: inflammatory bowel disease; Interleukin-10 gene-deficient mice; FTY720; Colonic lamina propria lymphocyte; Peyer's patch; Mesenteric lymph node; Lamina propria; IL-10^<-; ->マウス; FK506

Background & Aims: FTY72O is a novel lymphocyte homing agent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY72O is mediated by completely different mechanisms from those of conventional immunosuppressants, i.e., by accelerated lymphocyte homing. Interleukin-10 gene- deficient (IL-10^<-/->) mice spontaneously develop an enterocolitis by 2-3 months of age that has many histologic similarities to human Crohn' sdisease. In this study, we examined the efficacy of FTY72O in the treatmentof chronic colitis in an IL-10 ^<-/-> mouse model.Methods: FTY72O was administered orally at a dose of 0.3 mg/kg/day for 4 weeks to 16-20-wk-old IL-10^<-/-> mice with clinical signs of colitis. The gross and histologic appearance of the colon, the numbers and phenotype of lamina propria lymphocytes, and cytokine production by the lymphocytes were compared with those characteristics in a control group.Results: Single-dose administration of FTY72O resulted in the sequestration of circulating lymphocytes within Peyer's patches and mesenteric lymph nodes, with a corresponding reduction in the numbers of lymphocytes in the peripheral blood. Four- week administration resulted in a significant decrease in the severity of colitis, accompanied by a significant reductionin the CD^<4+> lymphocyte subpopulation in the colonic lamina propria and in IFN-γ production by the colonic lymphocytes.Conclusions: FTY720, a novel lymphocyte homing agent, treatment of adult mice resulted in amelioration of established chronic colitis in IL-10^<-/->mice that have many similarities to human Crohn's disease.

背景与目的：FTY72O是一种新型淋巴细胞归巢制剂，具有较强的免疫抑制活性。FTY72O诱导的免疫抑制是由与传统免疫抑制剂完全不同的机制介导的，即加速淋巴细胞归巢。白介素10基因缺陷(IL-10)小鼠在2-3个月大时自发发展为小肠结肠炎，在组织学上与人类克罗恩病有许多相似之处。本研究采用IL-10小鼠模型，观察FTY72O对慢性结肠炎的治疗作用。方法：给16-20周龄有结肠炎临床症状的IL-10小鼠口服FTY72O 0.3 mg/kg/d，连续4周。结果：FTY72O单次给药可导致Peyer氏结和肠系膜淋巴结内循环淋巴细胞隔离，外周血中淋巴细胞数量减少。给药4周后，结肠炎的严重程度明显减轻，结肠固有层CD^&lt；4+&gt；淋巴细胞亚群和结肠淋巴细胞产生的干扰素-γ显著减少。结论：FTY720是一种新型淋巴细胞归巢药物，治疗成年小鼠的慢性结肠炎可明显改善IL-10；lt；-/-&gt；小鼠的慢性结肠炎。

项目成果

Yoshikawa M, Inoue Y, Mizushima T, Kimura T, Inoue M, Nezu R, Ito T, Matsuda H.: "Actual situation and problems about catheter care in patients with benign intestinal failure under home parenteral nutrition (HPN)"Gan To Kagaku Ryoho. 2002 Dec;29 Suppl 3.

Yoshikawa M、Inoue Y、Mizushima T、Kimura T、Inoue M、Nezu R、Ito T、Matsuda H.：“家庭肠外营养（HPN）下良性肠衰竭患者导管护理的实际情况和问题”Gan To Kagaku

Yoshikawa M, Inoue Y, Mizushima T, Kimura T, Inoue M, Nezu R, Ito T, Matsuda H.: "Actual situation and problems about catheter care in patients with benign intestinal failure under home parenteral nutrition (HPN)"Gan To Kagaku Ryoho.. 29 Suppl 3. 424-427

Yoshikawa M、Inoue Y、Mizushima T、Kimura T、Inoue M、Nezu R、Ito T、Matsuda H.：“家庭肠外营养（HPN）下良性肠衰竭患者导管护理的实际情况和问题”Gan To Kagaku

Okuda Y, Takahashi I, Kim JK, Ohta N, Iwatani K, Iijima H, Kai Y, Tamagawa H, Hiroi T, Kweon MN, Kawano S, Takeda K, Akira S, Sasaki Y, Hori M, Kiyono H.: "Related Articles Links Development of colitis in signal transducers and activators of transcription

奥田 Y、高桥 I、金 JK、太田 N、岩谷 K、饭岛 H、凯 Y、玉川 H、广井 T、Kweon MN、河野 S、武田 K、阿基拉 S、佐佐木 Y、堀 M、清野 H："

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