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The Role of transcription factor Eos in dendritic cells development in gut immunity

Research Project

Project/Area Number 15K07956
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionTokushima Bunri University

Principal Investigator

Ohoka Yoshiharu  徳島文理大学, 薬学部, 教授 (60303971)

Research Collaborator Nakatsuma Aya (Yokota Aya)  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords樹状細胞 / レチノイン酸 / RALDH2 / Eos / 転写因子 / Ikarosファミリー / 免疫寛容 / T細胞 / 腸管免疫 / Ikzf4 (EOS) / 腸管免疫系
Outline of Final Research Achievements

Retinal dehydrogenase 2 (RALDH2) encoded by Aldh1a2 plays key roles in generating RA in dendritic cells (DCs) in gut-related lymphoid organs. To identify gene involved in the regulation of Aldh1a2 gene expression, gene expression of GM-CSF/LPS-treated and untreated BM-DCs was measured using DNA microarray. We identified Eos (ikzf4) gene whose expression was up-regulated by GM-CSF/LPS treatment in BM-DCs. Eos is a member of a zinc-finger transcription factor of the Ikaros (ikzf1) family. Eos siRNA partially downregulated Aldh1a2 gene in GM-CSF/LPS-treated BM-DCs. The expression of Eos mRNA was observed in MLN-DC but not in SPL or PLN in a manner similar to Aldh1a2 mRNA. Furthermore, both Eos and RALDH2 mRNA is specifically expressed in MLN-DC subset, CD11b±CD8α-CD103+ which has been thought to be a retinoic acid-producing anti-inflammatory DCs. These results suggest that Eos may be involved in the regulation of Aldh1a2 gene expression in DCs in gut-related lymphoid organs.

Academic Significance and Societal Importance of the Research Achievements

腸管免疫系においては免疫反応の促進と抑制のバランスを保つことが重要であり、その乱れは様々なアレルギー疾患や炎症性腸疾患発症等を引き起こす。この腸管免疫系における免疫反応のバランスの制御には、ビタミンAの代謝物であるレチノイン酸が重要な役割を果たしており、その産生酵素RALDH2の発現制御機構に転写因子Ikarosファミリーに属するEos遺伝子が関与することが明らかになった。この成果は今後、アレルギー疾患や炎症性腸疾患発症等の治療を目的とした新たな創薬ターゲットの分子基盤構築に貢献することが期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2019 2016 2015 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Beta 1-integrin ligation and TLR ligation enhance GM-CSF-induced ALDH1A2 expression in dendritic cells, but differentially regulate their anti-inflammatory properties2016

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

      Sientific Reports

      Volume: 6 Issue: 1 Pages: 37914-37914

    • DOI

      10.1038/srep37914

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] h1、Th2サイトカイン遺伝子発現に対するレチノイン酸シグナルの解析2019

    • Author(s)
      岩倉裕璃、植松美月、岩田誠、中妻彩、大岡嘉治
    • Organizer
      日本薬学会 第139年会、幕張メッセ、千葉県
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトIL-13遺伝子発現に対するレチノイン酸シグナルの役割2019

    • Author(s)
      植松美月、岩倉裕璃、岩田誠、中妻彩、大岡嘉治
    • Organizer
      日本薬学会 第139年会、幕張メッセ、千葉県
    • Related Report
      2018 Annual Research Report
  • [Presentation] Contribution of GM-CSF to the RALDH2 expression in dendritic cells through two distinct pathways involving β-catenin and c-Rel.2016

    • Author(s)
      大岡 嘉治、中妻 彩、竹内 一、岩田誠
    • Organizer
      第89回日本生化学会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] GM-CSF induces RALDH2 expression in dendritic cells through two distinct pathways involving β-catenin and c-Rel2015

    • Author(s)
      OHOKA Yoshiharu, YOKOTA-NAKATSUMA Aya, TAKEUCHI Hajime, IWATA Makoto
    • Organizer
      日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Remarks] 徳島文理大学香川薬学部生体防御学講座

    • URL

      http://kp.bunri-u.ac.jp/kph05/gyoseki.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 徳島文理大学香川薬学部生体防御学講座ホームページ

    • URL

      http://kp.bunri-u.ac.jp/kph05/index.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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