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2002 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 13671301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

ITO Toshinori  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20231152)

Co-Investigator(Kenkyū-buntansha) KIYONO Hiroshi  The Institute of Medical Science The University of Tokyo, Professor, 医科学研究所, 教授 (10271032)
Project Period (FY) 2001 – 2002
Keywordsinflammatory bowel disease / Interleukin-10 gene-deficient mice / FTY720 / Colonic lamina propria lymphocyte / Peyer's patch / Mesenteric lymph node / Lamina propria
Research Abstract

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.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Inoue Y, Noro H, Komoda H, Kimura T, Mizushima T, Taniguchi E, Yumiba T, Itoh T, Ohashi S, Matsuda H.: "Related Articles, Links Completely laparoscopic total colectomy for chronic constipation : report of a case"Surg Today. 32(6). 551-554 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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. 424-427 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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 6 -deficient T-cell receptor alpha -deficient mice : a potential role of signal transducers and activators of transcription 6 -independent interleukin -4 signaling for the generation of Th2 -biased pathological CD4+ betabetaT cells"Am J Pathol. Jan;162(1). 263-271 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi I, Matsuda J, Gapin L, DeWinter H, Kai Y, Tamagawa H, Kronenberg M, Kiyono H.: "Related Articles, Links Colitis -related public T cells are selected in the colonic lamina propria of IL-10-deficient mice"Clin Immunol. Mar;102(3). 237-248 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kweon MN, Takahashi I, Yamamoto M, Jang MH, Suenobu N, Kiyono H.: "Development of antigen induced colitis in SCID mice reconstituted with spleen derived memory type CD4(+) CD45RB(+) T cells"Gut. Mar;50(3). 299-306 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kweon M, Takahashi I, Kiyono H.: "Related Articles, Links New insights into mechanism of inflammatory and allergic diseases in mucosal tissues (Review)"Digestion. 63 Suppl 1. 1-11 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue Y, Noro H, Komoda H, Kimura T, Mizushima T, Taniguchi E, Yumiba T, Itoh T, Ohashi S, Matsuda H.: "Completely laparoscopic total colectomy for chronic constipation: report of a case"Surg Today.. 32(6). 551-554 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kweon MN, Kiyono H.: "Eosinophilic gastroenteritis: a problem of the mucosal immune system"Curr Allergy Asthma Rep.. 3(1). 79-85 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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.: "Development of colitis in signal transducers and activators of transcription 6-deficient T-cell receptor alpha-deficient mice: a potential role of signal transducers and activators of transcription 6-independent interleukin-4 signaling for the generation of Th2-biased pathological CD4+ betabetaT cells"Am J Pathol.. 162(1). 263-271 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kinoshita N, Hiroi T, Ohta N, Fukuyama S, Park EJ, Kiyono H.: "Autocrine IL-15 mediates intestinal epithelial cell death via the activation of neighboring intraepithelial NK cells"J Immunol.. 169(11). 6187-6192 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagita M, Shimabukuro Y, Nozaki T, Yoshimura N, Watanabe J, Koide H, Terakura M, Saho T, Takedachi M, Jang MH, Kiyono H, Murakami S.: "IL-15 up-regulates iNOS expression and NO production by gingival epithelial cells"Biochem Biophys Res Commun.. 297(2). 329-334 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi I, Matsuda I, Gapin L, DeWinter H, Kai Y, Tamagawa H, Kronenberg M, Kiyono H.: "Colitis-related public T cells are selected in the colonic lamina propria of IL-10-deficient mice"Clin Immunol.. 102(3). 237-248 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kweon MN, Takahashi I, Yamamoto M, Jang MH, Suenobu N, Kiyono H.: "Development of antigen induced colitis in SCID mice reconstituted with spleen derived memory type CD4(+) CD45RB(+) T cells"Gut.. 50(3). 299-306 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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