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Identification of medullary thymic epithelial stem cells

Research Project

Project/Area Number 24590580
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

Hamazaki Yoko  京都大学, 医学(系)研究科(研究院), 准教授 (10362477)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords胸腺 / 中枢性自己寛容 / 胸腺上皮細胞 / 幹細胞 / 胸腺退縮 / 自己免疫疾患 / Aire / 自己寛容 / 胸腺上皮幹細胞
Outline of Final Research Achievements

Medullary thymic epithelial cells (mTECs) are crucial for central T cell self-tolerance. We demonstrate that implantation of embryonic TECs expressing claudin-3 and claudin-4 (Cld3,4) in a medulla-defective thymic microenvironment restores medulla formation and suppresses multiorgan autoimmunity throughout life. A minor SSEA-1(+) fraction within the embryonic Cld3,4(hi) TECs contained self-renewable clonogenic TECs, capable of preferentially generating mature mTECs in vivo. Adult SSEA-1(+)Cld3,4(hi) TECs retained mTEC reconstitution potential, although the activity decreased. The clonogenicity of TECs also declined rapidly after birth in wild-type mice, whereas it persisted in Rag2 knock out adult mice with defective thymopoiesis. The results suggest that unipotent mTEC-restricted stem cells that develop in the embryo have the capacity to functionally reconstitute the thymic medulla long-term, thus ensuring lifelong central T cell self-tolerance.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (32 results)

All 2016 2015 2014 2012 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Acknowledgement Compliant: 4 results,  Open Access: 7 results) Presentation (21 results) (of which Int'l Joint Research: 2 results,  Invited: 12 results) Remarks (1 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

    • Related Report
      2015 Annual Research Report
    • 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: - Issue: 4 Pages: 857-62

    • DOI

      10.1002/eji.201546253

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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 Issue: 11 Pages: 2985-93

    • DOI

      10.1002/eji.201545844

    • Related Report
      2015 Annual Research Report
    • 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 Issue: 7 Pages: 1432-43

    • DOI

      10.1016/j.celrep.2015.10.012

    • NAID

      120006727050

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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)
      1.Tahir S, Fukushima Y, Sakamoto K, Sato K, Fujita H, Inoue J, Uede T, Hamazaki Y, Hattori M, Minato N.
    • Journal Title

      The Journal of Immunology

      Volume: 194 Issue: 12 Pages: 5725-5735

    • DOI

      10.4049/jimmunol.1500319

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [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: 5 Issue: 1 Pages: 7978-7985

    • DOI

      10.1038/srep07978

    • NAID

      120005555511

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance.2014

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

      Immunity.

      Volume: 41 Issue: 5 Pages: 753-761

    • DOI

      10.1016/j.immuni.2014.10.011

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines.2014

    • Author(s)
      Mizuno, R., Kamioka, Y., Kabashima, K., Imajo, M., Sumiyama, K., Nakasho, E., Ito, T., Hamazaki, Y., Okuchi, Y., Sakai, Y., Kiyokawa, E., and Matsuda, M.
    • Journal Title

      J Exp Med

      Volume: 211 Issue: 6 Pages: 1123-36

    • DOI

      10.1084/jem.20132112

    • NAID

      120005439165

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine2014

    • Author(s)
      Nagatake T, Fujita H, Minato N, Hamazaki Y.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e90638-e90638

    • DOI

      10.1371/journal.pone.0090638

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis2012

    • Author(s)
      Fujita H, Hamazaki Y, Noda Y, Oshima M, and Minato N.
    • Journal Title

      PLOS ONE

      Volume: 7

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [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)
    • Place of Presentation
      Nichia Medical Hall, Kuramoto Campus, University of Tokushima
    • Year and Date
      2016-03-03
    • Related Report
      2015 Annual Research Report
    • 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
    • Place of Presentation
      RIKEN Yokohama Research Institute 6F seminar room
    • Year and Date
      2016-03-02
    • Related Report
      2015 Annual Research Report
    • 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
      2015-07-31
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 免疫系・内分泌系細胞に発現するクローディンとその意義2015

    • Author(s)
      濱崎 洋子
    • Organizer
      日本薬学会 第135年会 シンポジウム「上皮を標的とした創薬研究の新展開」
    • Place of Presentation
      神戸学院大学(神戸)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 免疫老化2015

    • Author(s)
      濱崎 洋子
    • Organizer
      日本抗加齢医学会 専門医・指導士認定委員会主催講習会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2015-03-22
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 中枢性免疫寛容を担う胸腺髄質上皮細胞の発生とその維持2015

    • Author(s)
      濱崎 洋子
    • Organizer
      第34回 日本胸腺研究会 ミニシンポジウム「胸腺の形成と維持 最近の話題」
    • Place of Presentation
      相模原市立市民・大学交流センター ユニコムプラザさがみはら
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Identification of medullary thymic epithelial stem cells ensuring lifelong central T-cell tolerance2014

    • Author(s)
      Yoko Hamazaki
    • Organizer
      第43回日本免疫学会学術集会 国際シンポジウム Thymic microenvironments for T cell development and repertoire formation
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Thymic microenvironments: Basics, Progress and Future2014

    • Author(s)
      濱崎 洋子
    • Organizer
      第43回日本免疫学会学術集会 オーバーヴュートーク
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] The 24th Hot Spring Harbor International Symposium2014

    • Author(s)
      Yoko Hamazaki
    • Organizer
      Thymic Medullary Epithelial Stem Cells Ensuring Lifelong Central T-cell Tolerance
    • Place of Presentation
      九州大学 生体防御医学研究所
    • Year and Date
      2014-11-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 中枢性免疫寛容を担う胸腺上皮細胞の発生とその維持2014

    • Author(s)
      濱崎 洋子
    • Organizer
      第一回皮膚免疫カンファレンス 特別講演
    • Place of Presentation
      六本木ヒルズ(東京)
    • Year and Date
      2014-07-19
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 中枢性免疫寛容を担う胸腺上皮細胞の発生とその維持2014

    • Author(s)
      濱崎 洋子
    • Organizer
      第51回日本消化器免疫学会総会 教育講演
    • Place of Presentation
      京都大学芝蘭会館
    • Year and Date
      2014-07-10
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Medullary thymic epithelial stem cells ensuring lifelong central T-cell tolerance

    • Author(s)
      Miho Sekai, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      6th International Workshop of Kyoto T Cell Conference (KTCC2013)
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Claudin-4ノックアウトマウスにおける尿路過形成と水腎症

    • Author(s)
      藤田春美、濱崎洋子、野田裕美、大島正信、湊長博
    • Organizer
      第65回 日本細胞生物学会大会
    • Place of Presentation
      ウインク愛知(名古屋)
    • Related Report
      2013 Research-status Report
  • [Presentation] Identification of thymic epithelial stem cells ensuring lifelong central T-cell tolerance

    • Author(s)
      Miho Sekai, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MiCo Milano Congressi (イタリア ミラノ)
    • Related Report
      2013 Research-status Report
  • [Presentation] Miho Sekai, Yoko Hamazaki, Nagahiro Minato

    • Author(s)
      Identification of thymic epithelial stem cells ensuring lifelong central T-cell tolerance
    • Organizer
      第42回日本免疫学会総会
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Research-status Report
  • [Presentation] Medullary thymic epithelial stem cells ensuring lifelong central T-cell tolerance

    • Author(s)
      Yoko Hamazaki
    • Organizer
      第42回日本免疫学会学術集会 国際シンポジウム
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis

    • Author(s)
      藤田 春美、濱崎 洋子、 野田 裕美、大島 正伸、湊 長博
    • Organizer
      第35回日本分子生物学会総会
    • Place of Presentation
      理化学研究所 免疫・アレルギー科学総合研究センター  (横浜)
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of thymic epithelial stem cells ensuring lifelong central T-cell tolerance

    • Author(s)
      Miho Sekai, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      第41回日本免疫学会総会(口頭発表)
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Claudin-5 is a Crucial Component of Blood-thymus Barrier by Regulating Vascular Permeability

    • Author(s)
      Takahiro Nagatake, Yan-Chun Zhao, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第41回日本免疫学会総会(口頭発表)
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Claudin-5 plays a role in establishing specific thymic microenvironment by regulating vascular permeability.

    • Author(s)
      Takahiro Nagatake, Yan-Chun Zhao, Nagahiro Minato and Yoko Hamazaki
    • Organizer
      ThymUS international conference 2012 (口頭発表)
    • Place of Presentation
      Trump International Beach Resort、(アメリカ)
    • Related Report
      2012 Research-status Report
  • [Presentation] Miho Sekai, Yoko Hamazaki, Nagahiro Minato

    • Author(s)
      Identification of thymic epithelial stem cells ensuring lifelong central T-cell tolerance
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MiCo Milano Congressi (イタリア)
    • Related Report
      2012 Research-status Report
  • [Remarks] 京都大学 研究教育活動データベース

    • URL

      http://kyouindb.iimc.kyoto-u.ac.jp/j/mK8yN

    • Related Report
      2013 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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