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Analysis of the bioactive molecules that enhance the induction and suppressive properties of human regulatory T cells and application to therapy

Research Project

Project/Area Number 21591282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionEhime University

Principal Investigator

HASEGAWA Hitoshi  愛媛大学, 大学院・医学系研究科, 准教授 (40164826)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsRegulatory T cells / Foxp3 / lipids / Peroxisome proliferator-activated receptor / 制御性T細胞 / PPAR / 核内受容体リガンド / lysophosphatidylcholine
Research Abstract

We screened 14 kinds of the molecules that enhanced the induction and suppressive function of human regulatory T cells(Treg) from lipid and nuclear receptor ligand libraries. Of these, PPAR agonists increased suppressive function and expression of Foxp3 in induced Tregs(iTregs). PPAR agonist-treated iTregs increased demethylation level of the Foxp3 promoter region and CNS3. Moreover, TSA and ATRA enhanced iTregs generation synergistically with PPAR agonists. On the other hand, lysophosphatidylcholine(LPC) enhances Foxp3 expression and the suppressive function of nTregs through TGF-beta1 produced by nTregs themselves. These agents increased Treg differentiation and induction and may be benefical for the treatment of human autoimmune diseases.

Report

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

    (25 results)

All 2012 2011 2010 2009

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (17 results)

  • [Journal Article] Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-βproduction. Biochem2011

    • Author(s)
      Hasegawa H, Lei J, Matsumoto T, Onishi S, Suemori K, Yasukawa M
    • Journal Title

      Biophys. Res. Commun

      Volume: 415 Pages: 526-531

    • Related Report
      2011 Final Research Report
  • [Journal Article] Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-β production2011

    • Author(s)
      Hasegawa H, et al
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 415 Issue: 3 Pages: 526-531

    • DOI

      10.1016/j.bbrc.2011.10.119

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peroxisome proliferator-activated receptor alpha and gamma agonists together with TGF-beta convert human CD4+ CD25-T cells into functional Foxp3+ regulatory T cells2010

    • Author(s)
      Lei J., Hasegawa H, Matsumoto T, Yasukawa M
    • Journal Title

      J. Immunol

      Volume: 185 Pages: 7186-7198

    • Related Report
      2011 Final Research Report
  • [Journal Article] Human herpesvirus 6 infection impairs Toll-like receptor signaling2010

    • Author(s)
      Murakami Y, Tanimoto K, Fujiwara H, An J, Suemori K, Ochi T, Hasegawa H, Yasukawa M
    • Journal Title

      Virol. J

      Volume: 10

    • Related Report
      2011 Final Research Report
  • [Journal Article] Fractalkine expression and CD16+ monocyte accumulation in glomerular lesions : association with their severity and diversity in lupus models2010

    • Author(s)
      Nakatani K, Yoshimoto S, Iwano M, Asai O, Samejima K, Sakan H, Terada M, Hasegawa H, Nose M, Saito Y
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 299

    • Related Report
      2011 Final Research Report
  • [Journal Article] Peroxisome proliferator-activated receptor alpha and gamma agonists together with TGF-betaconvert human CD4+CD25- T cells into functional Foxp3+ regulatory T cells2010

    • Author(s)
      Lei J, Hasegawa H, et al.
    • Journal Title

      Journal of Immunology

      Volume: 185 Pages: 7186-7198

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fractalkine expression and CD16+ monocyte accumulation in glomerular lesions : Association with their severity and diversity in lupus models2010

    • Author(s)
      Nakatani K, Hasegawa H, et al.
    • Journal Title

      Am.J.Physiol.Renal.Physiol.

      Volume: 299

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human herpesvirus 6 infection impairs Toll-like receptor signaling2010

    • Author(s)
      Murakami Y, Hasegawa H, et al.
    • Journal Title

      Virol.J.

      Volume: 7 Pages: 91-91

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Analysis of the bioactive molecules that promote the induction of human tolerogenic dendritic cells and application to therapy for vasculitis2012

    • Author(s)
      Hasegawa H, et al
    • Organizer
      The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012
    • Place of Presentation
      Tokyo
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Lysophosphatidylcholine enhances suppressive function of human naturally occurring regulatory T cells through TGF-βproduction2011

    • Author(s)
      Hasegawa H, Lei J, Matsumoto T, Onishi S, Suemori K, Yasukawa M
    • Organizer
      75th Annual Scientific Meeting of the American College of Rheumatology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2011-11-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Lysophosphatidylcholine enhances suppressive function of human naturally occurring regulatory T cells through TGF-β production2011

    • Author(s)
      Hasegawa H, et al
    • Organizer
      75th Annual Scientific Meeting of the American College of Rheumatology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2011-11-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Analysis of the bioactive molecules that promote the induction of human tolerogenic dendritic cells2011

    • Author(s)
      Matsumoto T, Hasegawa H, Lei J, Onishi S, Suemori K, Yasukawa M
    • Organizer
      75th Annual Scientific Meeting of the American College of Rheumatology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2011-11-07
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ヒト制御性T細胞の誘導におけるPPARアゴニストとTSAまたはATRAの併用による相乗効果2011

    • Author(s)
      長谷川均、金磊、松本卓也、大西佐知子、末盛浩一郎、安川正貴
    • Organizer
      第55回日本リウマチ学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2011-07-19
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ヒト免疫寛容樹状細胞の誘導を促進させる生理活性物質の探索2011

    • Author(s)
      松本卓也、長谷川均、金磊、大西佐知子、末盛浩一郎、安川正貴
    • Organizer
      第55回日本リウマチ学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2011-07-18
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Antagonist of CXCL16 ameliorates the progression of vasculitis in arteritis-prone McH5/lpr mice2011

    • Author(s)
      Hasegawa H, Miyazaki T, Lei J, Matsumoto T, Nose M, Yasukawa M
    • Organizer
      19th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-05-26
    • Related Report
      2011 Final Research Report
  • [Presentation] Antagonist of CXCL16 ameliorates the progression of vasculitis in arteritis-prone McH5/1pr mice2011

    • Author(s)
      Hasegawa H, et al
    • Organizer
      19th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      Osaka
    • Year and Date
      2011-05-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] CXCL16 antagonist ameliorates the progression of vasculitis in McH5/lpr mice2010

    • Author(s)
      Hasegawa H, et al.
    • Organizer
      74^<th> Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2010-11-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Peroxisome proliferator-activated receptorαandγagonists together with TGF-βconvert human CD4+ CD25-T cells into functional Foxp3+ regulatory T cells2010

    • Author(s)
      Hasegawa H, Lei J, Matsumoto T, Yasukawa M
    • Organizer
      74^<th> Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2010-11-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Peroxisome proliferator-activated receptor alpha and gamma agonists together with TGF-beta convert human CD4+CD25- T cells into functional Foxp3+ regulatory T cells2010

    • Author(s)
      Hasegawa H, et al.
    • Organizer
      74^<th> Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2010-11-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] PPARαおよびγアゴニストによるヒト制御性Τ細胞への分化誘導機序2010

    • Author(s)
      金磊、長谷川均、松本卓也、河野政志、安川正貴
    • Organizer
      第54回日本リウマチ学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2010-04-23
    • Related Report
      2011 Final Research Report
  • [Presentation] PPARalphaおよびgammaアゴニストによるヒト制御性T細胞への分化誘導機序2010

    • Author(s)
      金嘉、長谷川均, 他
    • Organizer
      第54回日本リウマチ学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] PPARαおよびγアゴニストによるヒト制御性T細胞への分化誘導機序2010

    • Author(s)
      金磊, 長谷川均, 他
    • Organizer
      第54回日本リウマチ学会総会
    • Place of Presentation
      神戸ポートピアホテル(神戸)
    • Year and Date
      2010-04-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] PPARαおよびPPARγアゴニストはヒト制御性T細胞への誘導や機能を増強する2009

    • Author(s)
      長谷川均、金磊、河野政志、松本卓也、安川正貴
    • Organizer
      第39回日本免疫学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-12-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Peroxisome proliferator-activated receptor α and γ agonists enhance human regulatory T cell function and induction2009

    • Author(s)
      長谷川均, et al.
    • Organizer
      第39回日本免疫学会総会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Amelioration of lupus nephritis with dendritic cell using a NF-kappaB decoy and histone H3 peptide in NZB/W F1 mice2009

    • Author(s)
      長谷川均, et al.
    • Organizer
      The 75^<th> Annual Scientific Meeting of the American College of Rheumatolagy
    • Place of Presentation
      Philadelphia, U.S.A.
    • Year and Date
      2009-10-19
    • Related Report
      2009 Annual Research Report

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

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