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The role of TL1A in inflammatory bowel disease

Research Project

Project/Area Number 21790690
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKurume University

Principal Investigator

TAKEDATSU Hidetoshi  Kurume University, 医学部, 助教 (80352144)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords炎症性腸疾患 / TL1A / death receptor 3 / Death receptor 3
Research Abstract

The pathogenicrole of TL1A in inflammatory bowel disease has been shown in several studies. In this study, we evaluated the role of TL1A in acute colitis and the association between TL1A and Th2.
We showed that TL1A expression from macrophages and DR3 expression from intestinal epithelial cells was increased in DSS-colitis mice. In human intestinal epithelial cell lines, DR3 expression was increased by the stimulation of IL-1 and IL-6. Indeed, DR3 expression was increased in intestinal epithelial cells from Crohn's Disease patients compared with normal and ulcerative colitis. These results suggested that the interaction of TL1A and DR3 on intestinal epithelial cells was important to develop acute colitis. Then, we performed the treatment of neutralizing anti-TL1A antibodies in DSS acute colitis. Anti-TL1A treatment attenuated acute colitis, however there was not a significant difference of body weight, colon length, and cytokine expression between control group and treatment group. We made siRNA of TL1A because we could not have an enough amount of anti-TL1A antibodies. We are going to continue to study the treatment of siRNA in DSS acute colitis.
Furthermore, we investigated whether TL1A activated Th2 cells. In our study, SAMP1/Yit mice which spontaneously develop severe ileitis, were used. TL1A was significantly increased in ileum of SAMP1/Yit mice. Mononuclear cells isolated from mesenteric lymph nodes were stimulated with TL1A, IL-12, IL-23, IL-13 and their combinations. In this experiment, we showed that TL1A activated not only Th1and Th17, but also Th2 cells.

Report

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

    (7 results)

All 2010 2009 Other

All Journal Article (2 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] 炎症性腸疾患におけるTL1A(TNFSF15)の役割と抗TL1A抗体による治療効果2010

    • Author(s)
      竹田津英稔、光山慶一、佐田通夫
    • Journal Title

      消化器内科 Vol.51No.4

      Pages: 353-360

    • Related Report
      2010 Final Research Report
  • [Journal Article] 炎症性腸疾患におけるTL1A(TNFSF15)の役割と抗TL1A抗体による治療効果2010

    • Author(s)
      竹田津英稔
    • Journal Title

      消化器内科

      Volume: 51 Pages: 353-360

    • Related Report
      2010 Annual Research Report
  • [Presentation] Constitutive in vivo expression of TL1A (TNFSF15) in myeloid or lymphoid cells induce mild small bowel inflammation in mice2010

    • Author(s)
      David Q.Shih
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      New Orleans USA
    • Year and Date
      2010-05-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Constitutive in vivo expression of TL1A (TNFSF15) in myeloid or lymphoid cells induce mild small bowel inflammation in mice DDW-USA2010

    • Author(s)
      David Q.Shih, Robert Barrett, Xiaolan Zhang, Brian Ko, Michelle H.Wong Piangwarin Phaosawasdi, Nicole Yeager, Gislaine Martins, Hidetoshi Takedatsu, Kathrin S.Michelsen, Stephan R.Targan
    • Organizer
      The 111st American Gastroenterological Association Institute
    • Related Report
      2010 Final Research Report
  • [Presentation] 炎症性腸疾患におけるTL1Aの役割と抗TL1A抗体による治療効果の検討2009

    • Author(s)
      竹田津英稔
    • Organizer
      第17回 日本消化器関連学会週間
    • Place of Presentation
      グランドプリンスホテル京都
    • Year and Date
      2009-10-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 炎症性腸疾患におけるTL1Aの役割と抗TL1A 抗体による治療効果の検討2009

    • Author(s)
      竹田津英稔
    • Organizer
      JDDW(第51回日本消化器病学会大会)シンポジウム
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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

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