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2014 Fiscal Year Annual Research Report

免疫老化、自己免疫疾患発症における胸腺髄質上皮細胞の変容とその意義

Publicly Offered Research

Project AreaAnalysis and synthesis of multi-dimensional immune organ network
Project/Area Number 25111505
Research InstitutionKyoto University

Principal Investigator

濱崎 洋子  京都大学, 医学(系)研究科(研究院), 准教授 (10362477)

Project Period (FY) 2013-04-01 – 2016-03-31
Keywords胸腺 / 胸腺上皮細胞 / 幹細胞
Outline of Annual Research Achievements

昨年度までに、自己寛容を保証する胸腺髄質上皮幹細胞の存在を証明し、かつその活性が生後直後に急速に低下することが明らかとなり、それらの点について論文としてまとめることができた。本年度は、中枢性自己寛容を担う髄質上皮細胞の何らかの異常と、自己免疫疾患発症との関連を様々な自己免疫モデルマウスを用いて検討した。その結果、全身性自己免疫疾患であるSLEのマウスモデルが、髄質上皮細胞の発生異常を呈することが明らかとなった。 そこで、胸腺髄質上皮幹細胞の同定とその活性の評価に大きな役割を果たした培養系を用いて、本マウスの胸腺上皮コロニー形成能について検討したところ、B6マウスと比較して新生児の時点て明らかにコロニー形成能が低いことが分かった。以上の結果は、SLEモデルマウスで認められるT細胞の機能異常が、胸腺髄質上皮細胞の発生異常に起因する可能性があること、またこの発生異常が幹細胞レベルで起こっている可能性を示唆するものである。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

  • Research Products

    (9 results)

All 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 5 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution2016

    • Author(s)
      Hamazaki Y, Sekai M, Minato N.
    • Journal Title

      Immunol Rev.

      Volume: 印刷中 Pages: 印刷中

    • DOI

      -

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK+ medullary epithelial progenitors.2016

    • Author(s)
      Baik S, Sekai M, Hamazaki Y, Jenkinson WE, Anderson G.
    • Journal Title

      Eur J Immunol.

      Volume: 印刷中 Pages: 印刷中

    • DOI

      doi: 10.1002/eji.201546253.

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Adult thymic epithelial cell (TEC) progenitors and TEC stem cells – Models and mechanisms for the development and maintenance of thymic epithelial cells2015

    • Author(s)
      Hamazaki Y.
    • Journal Title

      Eur J Immunol.

      Volume: 45 Pages: 2985-93

    • DOI

      doi: 10.1002/eji.201545844.

    • Peer Reviewed / Acknowledgement Compliant
  • [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 Pages: 1432-43.

    • DOI

      doi: 10.1016/j.celrep.2015.10.012.

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A CD153+CD4+ T Follicular Cell Population with Cell-Senescence Features Plays a Crucial Role in Lupus Pathogenesis via Osteopontin Production.2015

    • Author(s)
      Tahir S, Fukushima Y, Sakamoto K, Sato K, Fujita H, Inoue J, Uede T, Hamazaki Y, Hattori M, Minato N.
    • Journal Title

      J Immunol.

      Volume: 194 Pages: 5725-35.

    • DOI

      doi: 10.4049/jimmunol.1500319.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia.2015

    • Author(s)
      Doi K, Imai T, Kressler C, Yagita H, Agata Y, Vooijs M, Hamazaki Y, Inoue J, Minato N.
    • Journal Title

      Sci Rep.

      Volume: 23 Pages: 7978.

    • DOI

      doi: 10.1038/srep07978.

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Medullary thymic epithelial stem cells ensuring lifelong T-cell tolerance2016

    • Author(s)
      Yoko Hamazaki
    • Organizer
      The Fifth Bizan Immunology Symposium at University of Tokushima (BISUT5) “Immune System Development, Deviation, and Regulation”
    • Place of Presentation
      Nichia Medical Hall, Kuramoto Campus, University of Tokushima (Tokushima)
    • Year and Date
      2016-03-03
    • Int'l Joint Research / Invited
  • [Presentation] Medullary Thymic Epithelial Stem Cells Ensuring Lifelong Central T cell Tolerance2016

    • Author(s)
      Yoko Hamazaki
    • Organizer
      Environment controlling normal and diseased hematopoietic and immune systems (Sponsored by MEXT Research Project on Analysis and Synthesis of Multidimensional Immune Organ Network and RIKEN IMS)
    • Place of Presentation
      RIKEN Yokohama Research Institute 6F seminar room (Yokohama)
    • Year and Date
      2016-03-02
    • Int'l Joint Research / Invited
  • [Presentation] 胸腺における中枢性自己寛容の成立と胸腺退縮に伴うT細胞の加齢変化2015

    • Author(s)
      濱崎洋子
    • Organizer
      CREATE 2015(Cardio-Renal Interaction and Translational Research Enhancement)
    • Place of Presentation
      ロイヤルパークホテル(東京)
    • Year and Date
      2015-09-25
    • Invited

URL: 

Published: 2017-01-06  

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