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Molecular mechanism of the development of thymic epithelial cells

Research Project

Project/Area Number 15K19130
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionThe University of Tokushima

Principal Investigator

OHIGASHI Izumi  徳島大学, 先端酵素学研究所(プロテオ), 准教授 (00596588)

Research Collaborator TAKAHAMA Yousuke  
SAKATA Mie  
UDDIN Myn  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords胸腺 / 獲得免疫 / 胸腺上皮細胞
Outline of Final Research Achievements

The thymus is an organ that produces functionally competent T cells that protect us from pathogens and malignancies. Foxn1 is a transcription factor that is essential for thymus organogenesis; however, the direct target for Foxn1 to actuate thymic T cell production is unknown. Here we show that a Foxn1-binding cis-regulatory element promotes the transcription of β5t, which has an essential role in cortical thymic epithelial cells to induce positive selection of functionally competent CD8+ T cells. A point mutation in this genome element results in a defect in β5t expression and CD8+ T cell production in mice. The results reveal a Foxn1-β5t transcriptional axis that governs CD8+ T cell production in the thymus

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Generation of diversity in thymic epithelial cells.2017

    • Author(s)
      Takahama Y, Ohigashi I, Baik S, Anderson G.
    • Journal Title

      Nat Rev Immunol

      Volume: 印刷中 Issue: 5 Pages: 295-305

    • DOI

      10.1038/nri.2017.12

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Foxn1-β5t transcriptional axis controls CD8+ T cell production in the thymus.2017

    • Author(s)
      Uddin MM, Ohigashi I, Motosugi R, Nakayama T, Sakata M, Hamazaki J, Nishito Y, Rode I, Tanaka K, Takemoto T, Murata S, Takahama Y.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 14419-14419

    • DOI

      10.1038/ncomms14419

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Dynamic spatio-temporal contribution of single b5t+ cortical epithelial precursors to the thymus medulla2016

    • Author(s)
      Mayer CE, Zuklys S, Zhanybekova S, Ohigashi I, Teh HY, Sansom SN, Shikama-Dorn N, Hafen K, Macaulay IC, Deadman ME, Ponting CP, Takahama Y, Hollander GA.
    • Journal Title

      European Journal of Immunology

      Volume: 46 Issue: 4 Pages: 846-856

    • DOI

      10.1002/eji.201545995

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Development and developmental potential of cortical thymic epithelial cells2016

    • Author(s)
      Ohigashi I, Kozai M, Takahama Y
    • Journal Title

      Immunological Reviews

      Volume: 271 Pages: 10-22

    • NAID

      120006727049

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Flow cytometry analysis of thymic epithelial cells and their subpopulation2016

    • Author(s)
      Ohigashi I, Takahama Y
    • Journal Title

      Methods in Molecular Biology

      Volume: 1323 Pages: 65-73

    • DOI

      10.1007/978-1-4939-2809-5_5

    • ISBN
      9781493928088, 9781493928095
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adult thymic medullary epithelium is maintained and regenerated by lineage-restricted cells rather than bipotent progenitors2015

    • Author(s)
      Ohigashi I, Zuklys S, Sakata M, Mayer CE, Hamazaki Y, Minato N, Hollander GA, Takahama Y.
    • Journal Title

      Cell Rep.

      Volume: 13 Issue: 7 Pages: 1432-43

    • DOI

      10.1016/j.celrep.2015.10.012

    • NAID

      120006727050

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Foxn1-binding cis-regulatory element required for optimal CD8+ T cell production in the thymus2017

    • Author(s)
      Izumi Ohigashi, Myn Uddin, Tatsuya Takemoto, Yousuke Takahama
    • Organizer
      11th International Symposium of the institute network
    • Place of Presentation
      徳島大学藤井記念ホール(徳島県・徳島市)
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] CCL21 regulates T-cell self-tolerance in thymic medulla2017

    • Author(s)
      Mina Kozai, Izumi Ohigashi, Yousuke Takahama
    • Organizer
      11th International Symposium of the institute network
    • Place of Presentation
      徳島大学藤井記念ホール(徳島県・徳島市)
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Foxn1-binding cis-regulatory element required for optimal CD8+ T cell production in the thymus2016

    • Author(s)
      Ohigashi Izumi
    • Organizer
      5th Bizan symposium
    • Place of Presentation
      徳島大学日亜メディカルホール(徳島県・徳島市)
    • Year and Date
      2016-03-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胸腺におけるCD8+ T細胞生成を制御するFoxn1結合シス制御領域の同定2016

    • Author(s)
      大東いずみ, 竹本龍也, 高浜洋介
    • Organizer
      第39回分子生物学学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] The spatio-temporal activation of Wnt/β-catenin signaling in the thymic epithelial cells in mouse thymus2016

    • Author(s)
      Sayumi Fujimori, Izumi Ohigashi, Tatsuya Takemoto, Yousuke Takahama, Shinji Takada
    • Organizer
      第39回分子生物学学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Foxn1-binding cis-regulatory element for optimal CD8+ T cell production in the thymus2016

    • Author(s)
      Myn Uddin, Izumi Ohigashi, Yousuke Takahama
    • Organizer
      第26回 Kyoto T cell Conference
    • Place of Presentation
      延暦寺会館(京都府・京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] The differentiation potential of β5t+ thymic epithelial progenitors2015

    • Author(s)
      Ohigashi Izumi, Takahama Yousuke
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 成体の胸腺髄質上皮は髄質系列細胞によって維持・再生される2015

    • Author(s)
      大東いずみ、髙濵洋介
    • Organizer
      Kyoto T cell Conference 第25回学術集会
    • Place of Presentation
      京都大学芝蘭会館(京都府・京都市)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Book] Encyclopedia of Immunobiology2016

    • Author(s)
      Ohigashi I, Takahama Y.
    • Total Pages
      3126
    • Publisher
      Elsevier
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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