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Development of novel immunotherapies using retinoid X agonists

Research Project

Project/Area Number 23590317
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionTokushima Bunri University

Principal Investigator

TAKEUCHI Hajime  徳島文理大学, 薬学部, 准教授 (00421298)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsRXRアゴニスト / Th17 / 制御性T細胞 / レチノイン酸 / EAE / RXRシグナル / RXR
Research Abstract

Retinoic acid (RA) enhances TGF-beta-dependent differentiation of Foxp3+ inducible regulatory T cells (iTreg) and inhibits Th17 differentiation by binding to the retinoic acid receptor (RAR). It remained unclear if RXR-mediated stimulation affected the iTreg and Th17 differentiation. We found here that the RXR agonists augmented the ability of RA or the RAR agonist to enhance CD4+CD25- T cells to acquire Foxp3 expression and suppressive function.
RXR agonists alone suppressed ROR-gamma-t mRNA and IL-17 expression. The combination of an RXR agonist and RA additively suppressed Th17 differentiation when the concentration of RA was low. Accordingly, continuous treatment with an RXR agonist ameliorated experimental autoimmune encephalomyelitis. These results suggest that RXR stimulation enhances RAR-dependent and independent modulation of Foxp3+ iTreg and Th17 differentiation, respectively.

Report

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

    (13 results)

All 2013 2012 2011 Other

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (8 results) Remarks (2 results)

  • [Journal Article] Retinoid X receptor agonists modulate Foxp3+ regulatory T cell and Th17 cell with differential dependence on retinoic acid receptor activation2013

    • Author(s)
      Takeuchi, H., Yokota-Nakatsuma, A., Ohoka, Y., Kagechika, H., Kato, C., Song S.Y., Iwata M.
    • Journal Title

      J Immunol

      Volume: 191 Pages: 3725-3733

    • Related Report
      2013 Final Research Report
  • [Journal Article] Retinoid X Receptor Agonists Modulate Foxp3 + Regulatory T Cell and Th17 Cell Differentiation with Differential Dependence on Retinoic Acid Receptor Activation.2013

    • Author(s)
      Takeuchi, H.; Yokota-Nakatsuma, A.; Ohoka, Y.; Kagechika, H.; Kato, C.; Si-Young Song, S.-Y.; Iwata, M.
    • Journal Title

      J. Immunol.

      Volume: 191 Issue: 7 Pages: 3725-3733

    • DOI

      10.4049/jimmunol.1300032

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 粘膜系リンパ球の腸管指向性獲得の分子メカニズム2011

    • Author(s)
      竹内 一、大岡嘉治、岩田 誠
    • Journal Title

      細胞工学

      Volume: 30 Pages: 381-386

    • Related Report
      2011 Research-status Report
  • [Presentation] Amplification of retinoic acid-dependent induction of Foxp3+ regulatory T cell differentiation by retinoid X receptor agonists and organotins2012

    • Author(s)
      Takeuchi, H., Yokota-Nakatsuma, A., Ohoka, Y., Kagechika, H., Iwata, M
    • Organizer
      第41回日本免疫学会学術総会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 制御性T細胞分化におけるRXRシグナルの影響2011

    • Author(s)
      竹内一、横田彩、大岡嘉治、岩田誠
    • Organizer
      日本免疫学会
    • Place of Presentation
      千葉
    • Related Report
      2011 Research-status Report
  • [Presentation] 制御性T細胞分化におけるRXRシグナルの影響

    • Author(s)
      竹内一, 横田彩, 大岡嘉治, 岩田誠
    • Organizer
      第40回日本免疫学会
    • Related Report
      2013 Final Research Report
  • [Presentation] Amplification of retinoic acid-dependent induction of Foxp3^+ regulatory T cell differentiation by retinoid X receptor agonists and organotins

    • Author(s)
      竹内一, 中妻彩, 大岡嘉治, 影近弘之, 岩田誠
    • Organizer
      第41回日本免疫学会
    • Related Report
      2013 Final Research Report
  • [Presentation] haracterization of the role of retinoid X receptor signaling in the differentiation of Th17

    • Author(s)
      Takeuchi, H., Yokota-Nakatsuma, A., Ohoka, Y., Kagechika, H., Song, S-Y., Iwata, M.
    • Organizer
      第42回日本免疫学会
    • Related Report
      2013 Final Research Report
  • [Presentation] 制御性T細胞分化におけるRXRシグナルの影響

    • Author(s)
      竹内一, 中妻彩, 大岡嘉治, 影近弘之, 宋時栄, 岩田誠
    • Organizer
      第24回日本レチノイド研究会
    • Related Report
      2013 Final Research Report
  • [Presentation] 制御性T細胞分化におけるRXRシグナルの影響

    • Author(s)
      竹内一、中妻彩、大岡嘉治、影近弘之、宋時栄、岩田誠
    • Organizer
      第24回日本レチノイド研究会
    • Place of Presentation
      星薬科大学百年記念館
    • Related Report
      2013 Annual Research Report
  • [Presentation] Characterization of the role of retinoid X receptor signaling in the differentiation of Th17.

    • Author(s)
      2. Takeuchi H, Yokota-Nakatsuma A, Ohoka Y, Kagechika H, Song S-Y, and Iwata M.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ
    • Related Report
      2013 Annual Research Report
  • [Remarks] 徳島文理大学香川薬学部衛生薬学講座ホームページ

    • URL

      http://kp.bunri-u.ac.jp/kph/index-14.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 徳島文理大学香川薬学部衛生薬学講座ホームページ

    • URL

      http://kp.bunri-u.ac.jp/kph/index-14.html

    • Related Report
      2013 Annual Research Report

URL: 

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

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