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Injection therapy of regulatory T cells into intestinal lumen

Research Project

Project/Area Number 21590804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TOTSUKA Teruji  東京医科歯科大学, 医学部, 非常勤講師 (70447465)

Co-Investigator(Kenkyū-buntansha) WATANABE Mamoru  東京医科歯科大学, 医歯薬総合研究科, 教授 (10175127)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords注腸療法 / 腸管局所療法 / 抑制性CD4+CD25+T細胞 / CD4^+CD45RB^<high> T細胞移入大腸炎モデ / 炎症性腸疾患 / CD4^+CD45RB^<high>T細胞移入大腸炎モデル
Research Abstract

A lot of young people are suffering from the inflammatory bowel disease(ulcerative colitis and Crohn's disease) that is an intractable disease to be forced to continuation of the treatment by over a life. Many cases of the inflammatory bowel disease are understood as autoimmune disease treated by nonspecific immune control medicine including a steroid and the immunosuppressive drug. However, there is a limit by the current medicine because of the resistance for the treatment. Recent reports suggest that the egress of effector or memory CD4+and CD8+T cells into the draining lymph nodes from the lung7 and of B cells and naive or memory CD4+and CD8+T cells into the popliteal lymph nodes from the footpad of skin8 requires the expression of CCR7 on these cells. In the intestine, however, the unique phenotype(CCR9 or integrinα4β7 orαEβ7-expressing cells) of the resident memory T cells and the lack of such cells elsewhere suggest that memory T cells in the intestinal lamina propria(LP) and intraepithelial space are tissue bound and do not exit the intestine, 1 but this theory remains unproven experimentally. The intrarectal administration of cells employed in this study was suggested by the fact that intratracheal instillation of cells in mice can induce their cell migration to the lung and thereafter to the blood systemically. 6 In this paper, we demonstrate that living CD4+T cells can not only penetrate intestinal barriers from the lumen to the LP but also constantly egress from the LP to the bloodstream constantly in a CCR7-and sphingosine 1-phosphate 1(S1P1)-independent manner.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (26 results)

All 2012 2011 2010 2009

All Journal Article (18 results) (of which Peer Reviewed: 8 results) Presentation (6 results) Book (2 results)

  • [Journal Article] The development of colitogenic CD4+T cells is regulated by IL-7 in collaboration with natural killer cell function in a murine model of colitis2012

    • Author(s)
      Yamaji O, Totsuka T
    • Journal Title

      J Immunol

      Volume: 188 Pages: 2524-2536

    • Related Report
      2011 Final Research Report
  • [Journal Article] The development of colitogenic CD4+ T cells is regulated by IL-7 in collaboration with natural killer cell function in a murine model of colitis2012

    • Author(s)
      Yamaji O, Totsuka T
    • Journal Title

      J Immunol

      Volume: 188 Issue: 6 Pages: 2524-2536

    • DOI

      10.4049/jimmunol.1100371

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Luminal CD4+T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation2011

    • Author(s)
      Nemoto Y, Watanabe M
    • Journal Title

      Gastroenterology

      Volume: 141 Pages: 2130-2139

    • Related Report
      2011 Final Research Report
  • [Journal Article] Upregulated IL-7 Receptor{ alpha} Expression on Colitogenic Memory CD4+T Cells May Participate in the Development and Persistence of Chronic Colitis2011

    • Author(s)
      Shinohara T, Nemoto Y, Totsuka T, et al
    • Journal Title

      Eur J Immunol

      Volume: 186 Pages: 2623-2632

    • Related Report
      2011 Final Research Report
  • [Journal Article] Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation2011

    • Author(s)
      Nemoto Y, Watanabe M
    • Journal Title

      Gastroenterology

      Volume: 141 Issue: 6 Pages: 2130-2139

    • DOI

      10.1053/j.gastro.2011.08.035

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-2 is positively involved in the development of colitogenic CD4+IL-7R alpha high memory T cells in chronic colitis2010

    • Author(s)
      Kameyama K, Totsuka T, Watanabe M, et al
    • Volume
      183
    • Pages
      2423-2436
    • Related Report
      2011 Final Research Report
  • [Journal Article] Prevalence of metabolic syndrome is comparable between inflammatory bowel disease patients and the general population2010

    • Author(s)
      Nagahori M, Hyun SB, Totsuka T, et al
    • Journal Title

      J Gastroenterol

      Volume: 45 Pages: 1008-1013

    • NAID

      10027699223

    • Related Report
      2011 Final Research Report
  • [Journal Article] Upregulated IL-7 Receptor {alpha} Expression on Colitogenic Memory CD4+ T Cells May Participate in the Development and Persistence of Chronic Colitis.2010

    • Author(s)
      Shinohara T, Nemoto Y, Totsuka T, et al
    • Journal Title

      J Immunol

      Volume: in press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-2 is positively involved in the development of co litogenic CD4+ IL-7R alpha high memory T cells in chronic colitis.2010

    • Author(s)
      Kameyama K, Totsuka T, Watanabe M, et al
    • Journal Title

      Eur J Immunol

      Volume: 183 Pages: 2423-2436

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of metabolic syndrome is comparable between inflam matory bowel disease patients and the general population.2010

    • Author(s)
      Nagahori M, Hyun SB, TotsukaT, et al
    • Journal Title

      J Gastroenterol.

      Volume: 45 Pages: 1008-1013

    • NAID

      10027699223

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+regulatory T cells in chronic colitis2009

    • Author(s)
      Totsuka T, Kanai T, Nemoto Y, et al
    • Journal Title

      J Immunol

      Volume: 182 Pages: 6079-6087

    • Related Report
      2011 Final Research Report
  • [Journal Article] Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directoly involved in colitis-associated carcinogenesis2009

    • Author(s)
      Onizawa M, Nagaishi T, Totsuka T, et al
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 296 Pages: 850-859

    • Related Report
      2011 Final Research Report
  • [Journal Article] Long-lived colitogenic CD4+momory T cells residing outside the intestine participate in the perpetuation of chronic colitis2009

    • Author(s)
      Nemoto Y, Kanai T, Totsuka T, et al
    • Journal Title

      J Immunol

      Volume: 183 Pages: 5059-5068

    • Related Report
      2011 Final Research Report
  • [Journal Article] RANK-RANKL signaling pathway Is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis.2009

    • Author(s)
      Totsuka T, Kanai T, Nemoto Y, et al
    • Journal Title

      J Immunol. 182

      Pages: 6079-6087

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis.2009

    • Author(s)
      Onizawa M, Nagaishi T, Totsuka T, et al
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 296

      Pages: 850-859

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis.2009

    • Author(s)
      Nemoto Y, Kanai T, Totsuka T, et al
    • Journal Title

      J Immunol 183

      Pages: 5059-5068

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      戸塚輝治、金井隆典、渡辺守
    • Journal Title

      消化器と免疫 45号消化器疾患における自然免疫・獲得免疫のクロストーク 慢性大腸炎の発症と維持におけるIL-7の役割(日本消化器免疫学会)

      Pages: 47-51

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      戸塚輝治、渡辺守
    • Journal Title

      炎症と免疫(Vol.17 no.3)サイトカインと炎症性疾患・自己免疫疾患 その病態における役割と治療展開 炎症性腸疾患(解説)(先端医学社)

      Pages: 327-334

    • Related Report
      2009 Annual Research Report
  • [Presentation] 腸炎惹起性CD4^+IL-7Rα^<high>メモリーT細胞分化機構におけるIL-2の重要性2009

    • Author(s)
      石黒佳織、金井隆典、戸塚輝治, ほか
    • Organizer
      第51回日本消化器病学会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 炎症性腸疾患の発症/持続にはCD4^+T細胞におけるIL-7Rαが必須である2009

    • Author(s)
      篠原玉子、金井隆典、戸塚輝治, ほか
    • Organizer
      第51回日本消化器病学会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 腸炎惹起性CD4^+IL-7Rα^<high>メモリーT細胞分化機構におけるIL-2の重要性2009

    • Author(s)
      石黒佳織、金井隆典、戸塚輝治, 他
    • Organizer
      第51回 日本消化器病学会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] 炎症性腸疾患の発症/持続にはCD4^+T細胞におけるIL-7Rαが必須である2009

    • Author(s)
      篠原玉子、金井隆典、戸塚輝治, 他
    • Organizer
      第51回 日本消化器病学会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] Systemic, but not intersinal, IL-7 is essential for the development and persistence of Chronic Colitis2009

    • Author(s)
      Totsuka T
    • Organizer
      DDW2009
    • Place of Presentation
      Chicago
    • Year and Date
      2009-05-31
    • Related Report
      2011 Final Research Report
  • [Presentation] Systemic, but not intersinal, IL-7 is essential for the development and persistence of Chronic Colitis.2009

    • Author(s)
      戸塚輝治
    • Organizer
      DDW2009
    • Place of Presentation
      シカゴ
    • Year and Date
      2009-05-31
    • Related Report
      2009 Annual Research Report
  • [Book] 消化器疾患における自然免疫・獲得免疫のクロストーク慢性大腸炎の発症と維持におけるIL-7の役割2009

    • Author(s)
      戸塚輝治、金井隆典、渡辺守
    • Related Report
      2011 Final Research Report
  • [Book] サイトカインと炎症性腸疾患・自己免疫疾患その病態における役割と治療展開炎症性腸疾患(解説)2009

    • Author(s)
      戸塚輝治、渡辺守
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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