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The role of dsRNA sensor in dendritic cells in a tolerized model of Type 1 diabetes

Research Project

Project/Area Number 23590880
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionKobe University

Principal Investigator

YASUDA HISAFUMI  神戸大学, 保健学研究科, 教授 (50403233)

Co-Investigator(Kenkyū-buntansha) 横野 浩一  神戸大学, その他部局等, その他 (50144580)
原 賢太  神戸大学, 医学部附属病院, 講師 (70397826)
明嵜 太一  神戸大学, 医学部附属病院, その他 (80467662)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords1型糖尿病 / 免疫寛容 / 病原体感知センサー / 樹状細胞 / 1型糖尿病
Research Abstract

We found that administration of anti-Fas Ab completely suppressed diabetic onset in NOD mice as a type 1 diabetic mouse model. In addition, administration of bone marrow derived dendritic cells from Fas-deficient NOD-lpr mice which is diabetes-free also comletely protected from diabetes onset in NOD mice. To evaluate the role of TLR3 as dsRNA sensor of dendritic cells, administration n of poly (I:C) as TLR3 agonist in NOD mice was performed firstly. Low dose of poly(I:C) suppressed diabetes onset in NOD mice, whereas high dose of poly(I:C) accelerated diabetes onset in NOD mice. Next, to evaluate the role of TLR3 in a tolerized mouse model of type 1 diabetes, administartion of high dose of poly(I:C) was performed in tolerized mice. Surprisingly, we found that high dose of poly(I:C) induced diabetes and broke tolerance in tolerized NOD mice treated with anti-Fas Ab. We demonstrated the importance of dsRNA sensor in the development of type 1 diabetes.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (29 results)

All 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (11 results) Book (9 results) Remarks (1 results)

  • [Journal Article] Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination : a case report2012

    • Author(s)
      Yasuda H, Nagata M, Moriyama H, Kobayashi H, Akisaki T, Ueda H, Hara K, Yokono K
    • Journal Title

      Diabet Med

      Volume: 29(1) Pages: 88-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A case of an elderly patient with slowly progressive type 1 diabetes who developed severe nonocclusive mesenteric ischemia without predisposing events2012

    • Author(s)
      Hara K, Yasuda H, Arai T, Miyoshi S, Kubokawa O, Mori H, Akisaki T, Kido Y, Yokono K, Akita H
    • Journal Title

      Intern Med

      Volume: 51(9) Pages: 1065-8

    • NAID

      130002061802

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination: a case report.2012

    • Author(s)
      Yasuda H, Nagata M, Moriyama H, Kobayashi H, Akisaki T, Ueda H, Hara K, Yokono K.
    • Journal Title

      Diabet Med.

      Volume: 29 Issue: 1 Pages: 88-89

    • DOI

      10.1111/j.1464-5491.2011.03391.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acid.2012

    • Author(s)
      Nakamura A, Hara K, Yamamoto K, Yasuda H, Moriyama H, Hirai M, Nagata M, Yokono K
    • Journal Title

      Geriatr Gerontol Int.

      Volume: 12 Issue: 1 Pages: 131-139

    • DOI

      10.1111/j.1447-0594.2011.00729.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice2011

    • Author(s)
      Tai N, Yasuda H, Zhang L, Rodriguez-Pinto D, Yokono K, Wong FS, Sherwin R, Nagata M, Wen L
    • Journal Title

      Clin Immunol

      Volume: 139(3) Pages: 336-49

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acceleration of autoimmune diabetes in Rheb-congenic NOD mice withβ-cell-specific mTORC1 activation2011

    • Author(s)
      Sasaki H, Yasuda H, Moriyama H, Nakamura A, Shimizu M, Arai T, Nagata M, Hara K, Yokono K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 408(2) Pages: 306-11

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IL-10-Conditioned Dendritic Cells Prevent Autoimmune Diabetes in NOD and HumanizedHLA-DQ8/RIP-B7.1 Mice.2011

    • Author(s)
      Tai N, Yasuda H, Xiang Y, Zhang L, Rodriguez-Pinto D, Yokono K, Sherwin R, Wong FS, Nagata M, Wen L.
    • Journal Title

      Clin Immunol.

      Volume: 139 Issue: 3 Pages: 336-349

    • DOI

      10.1016/j.clim.2011.03.003

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acceleration of autoimmune diabetes in Rheb-congenic NOD mice with β-cell-specific mTORC1 activation2011

    • Author(s)
      Sasaki, et al
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 408 Issue: 2 Pages: 306-311

    • DOI

      10.1016/j.bbrc.2011.04.026

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] CGMによる膵腎同時移植後患者の血糖変動の検討2014

    • Author(s)
      中村友昭、廣田勇士、中島進介、西本祐希、安田尚史、松本逸平、具英成、坂口一彦、小川渉
    • Organizer
      第41回日本膵・膵島移植研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-03-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Poly(I:C)投与1型糖尿病関連マウスにおける糖尿病発症の検討2014

    • Author(s)
      清水まみ、安田尚史、勝田敦美、高橋和真、永田正男
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] 1型糖尿病関連マウスにおけるpoly(I : C)投与による1型糖尿病発症の検討2013

    • Author(s)
      清水まみ、安田尚史、勝田敦美、高橋和真、原賢太、永田正男、横野浩一
    • Organizer
      第11回1型糖尿病研究会
    • Place of Presentation
      軽井沢
    • Year and Date
      2013-10-26
    • Related Report
      2013 Final Research Report
  • [Presentation] FasL-Fasシグナルの1型糖尿病発症における役割の検討2013

    • Author(s)
      安田尚史、勝田敦美、清水まみ、佐々木弘智、原賢太、秋田穂束、横野浩一
    • Organizer
      第8回加齢医学研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-01-19
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 1型糖尿病関連マウスにおけるpoly(I:C)投与による1型糖尿病発症の検討2013

    • Author(s)
      清水まみ、安田尚史、勝田敦美、高橋和真、原賢太、永田正男、横野浩一
    • Organizer
      第11回1型糖尿病研究会
    • Place of Presentation
      軽井沢
    • Related Report
      2013 Annual Research Report
  • [Presentation] NODマウスにおける1型糖尿病発症に関連するSR-Aの役割の検討2012

    • Author(s)
      清水まみ、安田尚史、勝田敦美、中村晃、佐々木弘智、永田正男、原賢太、高橋和真、横野浩一
    • Organizer
      第10回1型糖尿病研究会
    • Place of Presentation
      唐津
    • Year and Date
      2012-11-03
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] poly(I : C)投与SR-A KO NODマウスでの1型糖尿病発症の検討2012

    • Author(s)
      清水まみ、安田尚史、中村晃、勝田敦美、佐々木弘智、荒井隆志、永田正男、原賢太、高橋和眞、横野浩一
    • Organizer
      第55回日本糖尿病学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2012-05-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Modified LDLがリガンドであるSR-Aの1型糖尿病発症への影響2012

    • Author(s)
      清水まみ、安田尚史、中村晃、勝田敦美、佐々木弘智、荒井隆志、永田正男、原賢太、横野浩一
    • Organizer
      第7回加齢医学研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-01-21
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] poly(I:C)投与SR-A KO NODマウスでの1型糖尿病発症の検討2012

    • Author(s)
      清水まみ、安田尚史、中村 晃、勝田敦美、佐々木弘智、荒井隆志、永田正男、原 賢太、高橋和真、横野浩一
    • Organizer
      第55回日本糖尿病学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 1型糖尿病発症におけるMSR-Aの役割の検討2011

    • Author(s)
      清水まみ、安田尚史、森山啓明、中村晃、勝田敦美、花野智苗、佐々木弘智、荒井隆志、永田正男、原賢太、横野浩一
    • Organizer
      第9回1型糖尿病研究会
    • Place of Presentation
      大磯
    • Year and Date
      2011-10-30
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] 膵β細胞特異的Rheb過剰発現NODマウスにおける1型糖尿病発症の検討2011

    • Author(s)
      佐々木弘智、安田尚史、森山啓明、清水まみ、中村晃、荒井隆志、永田正男、原賢太、横野浩一
    • Organizer
      第54回日本糖尿病学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2011-05-21
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Book] インスリン抗体, 臨床検査データブックLAB DATA2013-2014(監修高久史麿編集黒川清、春日雅人、北村聖)2013

    • Author(s)
      安田尚史
    • Total Pages
      330
    • Related Report
      2013 Final Research Report
  • [Book] 臨床検査データブック LAB DATA 2013-2014 インスリン抗体、グリコサミノグリカン2013

    • Author(s)
      安田 尚史
    • Total Pages
      3
    • Publisher
      医学書院
    • Related Report
      2012 Research-status Report
  • [Book] 注意を要するインスリン依存状態の治療, 高齢1型糖尿病の管理, 別冊プラクティスブリットル糖尿病の病態と治療・管理のコツ-進化する治療・広がる未来-2012

    • Author(s)
      安田尚史、横野浩一
    • Related Report
      2013 Final Research Report
  • [Book] 【最新臨床糖尿病学 下-糖尿病学の最新動向-】 ライフステージ・タイプ別糖尿病の病態と治療 高齢者糖尿病 認知機能障害を有する高齢者糖尿病の管理のあり方2012

    • Author(s)
      横野 浩一, 安田 尚史
    • Total Pages
      4
    • Publisher
      日本臨床
    • Related Report
      2012 Research-status Report
  • [Book] 【浮腫の鑑別・対処法・メカニズム】 薬剤性浮腫2012

    • Author(s)
      安田 尚史, 横野 浩一
    • Total Pages
      8
    • Publisher
      Fluid Management Renaissance
    • Related Report
      2012 Research-status Report
  • [Book] 高齢者診療のディベートセッション 在宅例の管理 「発熱」は入院精査すべきか在宅管理すべきか 「入院精査すべき」の立場で2012

    • Author(s)
      安田 尚史
    • Total Pages
      5
    • Publisher
      Geriatric Medicine
    • Related Report
      2012 Research-status Report
  • [Book] 【高齢者糖尿病と認知症-糖尿病ケアにおける問題点-】 糖尿病患者における認知症の対応 現状と将来への展望2012

    • Author(s)
      横野浩一、安田尚史
    • Total Pages
      7
    • Publisher
      プラクティス
    • Related Report
      2011 Research-status Report
  • [Book] ブリットル糖尿病の病態と治療・管理のコツ -進化する治療・広がる未来ー2012

    • Author(s)
      安田尚史、横野浩一
    • Total Pages
      7
    • Publisher
      別冊プラクティス
    • Related Report
      2011 Research-status Report
  • [Book] 【高齢者の糖尿病管理】 高齢者糖尿病の臨床的特徴2011

    • Author(s)
      安田尚史、横野浩一
    • Total Pages
      8
    • Publisher
      月刊糖尿病
    • Related Report
      2011 Research-status Report
  • [Remarks] 神戸大学研究者紹介システム

    • URL

      http://kuid.ofc.kobe-u.ac.jp/InfoSearch/html/researcher/researcher_JXk34a9Cig7O-IBQ3mbe3w_ja.html?backtoResultPath=PositionView.do

    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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