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Challenge to the cell therapy by reprogramming colitogenic memory T cells

Research Project

Project/Area Number 24659375
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

KANAI Takanori  慶應義塾大学, 医学部, 教授 (40245478)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords炎症性腸疾患 / Th17細胞 / Th1細胞 / 腸管免疫 / 遺伝子導入 / 制御性T細胞 / 細胞療法 / メモリーT細胞
Research Abstract

We reported that the persistence of colitogenic memory cells are responsible for recurrence of inflammatory bowel disease (IBD). This study aimed to investigate the regulation of the colitigenic memory cells, leading to the development of new therapy for suppression of IBD recurrence. The results of the study is as below: 1. Th17 cells were induced under the influence of Lymphoid tissue inducer-like cell, 2. Classical Th1 cells obtained colitogenesity in the presence of alternative Th1 cells, 3. Clostridium butyricum, which is used as probiotics, induced anti-inflammatory macrophages. These results suggest the involvement of various cell types in the development of chronic inflammation of IBD.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (4 results)

  • [Journal Article] Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predjspose the liver to inflammation.2014

    • Author(s)
      Mikami Y, Mizuno S, Nakamoto N, Hayashi A, Sujino T, Sato T, Kamada N, Matsuoka K, Hisamatsu T, Ebinuma H, Hibi T, Yoshimura A, Kanai T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 1 Pages: 1-1

    • DOI

      10.1371/journal.pone.0084619

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Single Strain of Clostridium butyricum Induces Intestinal I L-10-Producing Macrophages to Suppress Acute Exlperimental Colitis in Mice.2013

    • Author(s)
      Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T, Hlbi T, Roers A, Yagita H, Ohteki T, Yoshimura A, Kanai T.
    • Journal Title

      Cell Host Microbe

      Volume: 13 Issue: 6 Pages: 711-22

    • DOI

      10.1016/j.chom.2013.05.013

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Th1/Th17-Mediated Interstitial Pneumonia in Chronic Colitis Mice Independent of Intestinal Microbiota.2013

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

      J Immunol.

      Volume: 190 Issue: 12 Pages: 6616-6625

    • DOI

      10.4049/jimmunol.1202930

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4+ memory T cells.2013

    • Author(s)
      Nemoto Y, Nakamura T, Watanabe M et al
    • Journal Title

      Gut.

      Volume: 62 Issue: 8 Pages: 1142-1152

    • DOI

      10.1136/gutjnl-2012-302029

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation2013

    • Author(s)
      Uo M
    • Journal Title

      Gut

      Volume: in press Issue: 12 Pages: 1734-44

    • DOI

      10.1136/gutjnl-2012-303063

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cells administered intrarectally penetrate the intestinal barrier to break intestinal tolerance via Th2-medeiated colitis in mice.2013

    • Author(s)
      Handa T, Kanai T, Sato T, Mikami Y, Sujino T, Hayashi. A, Mizuno S, Matsumoto A, Hisamatsu T, Hibi T.
    • Journal Title

      Immunology Letters

      Volume: 150 Issue: 1-2 Pages: 123-9

    • DOI

      10.1016/j.imlet.2013.01.010

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T-helper 17 and Interleukin-17-Producing Lymphoid Tissue Inducer-Like T Cells Make Different Contributions to Colitis in Mice.2012

    • Author(s)
      Ono Y, Kanai T, Sujino T, Nemoto Y, Kanai Y, Mikami Y, Hayashi A, Matsumoto A, Takaishi H, Ogata H, Matsuoka K, Hisamatsu T, Watanabe M, Hibi T.
    • Journal Title

      Gastroenterology

      Volume: 143 Issue: 5 Pages: 1288-1297

    • DOI

      10.1053/j.gastro.2012.07.108

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ROR_Yt-dependent IL-17A-producing cells in the pathogenesis of intestinal inflammation.2012

    • Author(s)
      Kanai T, Mikami Y, Sujino T, Hisamatsu T, Hibi T.
    • Journal Title

      Mucosal Immunology

      Volume: 5 Issue: 3 Pages: 240-247

    • DOI

      10.1038/mi.2012.6

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The development of colitogenic CD4(+) T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis2012

    • Author(s)
      Yamaji O, Nagaishi T, Totsuka T, Onizawa M, Suzuki M, Tsuge N, Hasegawa A, Okamoto R, Tsuchiya K, Nakamura T, Arase H, Kanai T, Watanabe M.
    • Journal Title

      J Immunol

      Volume: 188 Issue: 4 Pages: 2524-36

    • DOI

      10.1152/ajpgi.00071.2008

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Colitogenic Th17 Cells may Help the Generation of Colitogenic RORγt-Independent ClassicalTh1 Cells2013

    • Author(s)
      Saigusa K, Kanai T, Sujino T, Handa T, Hayashi A, Mikami Y,Mizuno S, Matsumoto A, Matuoka Y, Sato T, Hisamatsu T, Hibi T.
    • Organizer
      16th International Congress of Mucosal Immunology
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2013-07-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Clostridium Butyricum Regulates IL-10 Production in Normal and Inflammatory Conditions Through Different Target Cells2013

    • Author(s)
      Hayashi A, Kanai T, Sato T, Mikami Y, Matsuoka K, Hisamatsu T, Yoshimura A, Kamada N, Yagita H, Hibi T.
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2013-05-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 炎症性腸疾患と健常にそれぞれ存在する腸管Th17細胞の決定的な相違の追求2012

    • Author(s)
      金井隆典、筋野智久、三上洋平、日比紀文
    • Organizer
      第40回日本臨床免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-09-27
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸管におけるRorgt依存的lnnate Lymphoid cells(lLCs)の機能解析及び炎症制御能の解明2012

    • Author(s)
      木村佳代子、金井隆典、林篤史、筋野智久、三上洋平、半田一己、松岡克善、佐藤俊朗、久松理一、日比紀文
    • Organizer
      第49回日本消化器病学会総会
    • Place of Presentation
      鹿児島
    • Year and Date
      2012-07-05
    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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