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Function of claudins in Aire-expressing medullary thymic epithelial cells

Research Project

Project/Area Number 22790458
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

HAMAZAKI Yoko  京都大学, 医学研究科, 准教授 (10362477)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsT細胞分化 / 胸腺 / 自己免疫疾患 / 胸腺上皮細胞 / クローディン / Aire / T細胞分化
Research Abstract

To investigate the function of claudin (Cld)-3, 4 in thymic epithelial cells, we first madesingle KO mice for each gene. There was no obvious defect in each single KO mice; thus we next tried to make double KO mice. Since the distance of each gene on genome is only 40Kbp, we made a strategy in which Cld3 Tg vector was introduced into Cld4KO ES cells. We have succeded in making double KO mice and now are analyzing the phenotypes on thymic organogenesis and T cell development.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (53 results)

All 2012 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (40 results) (of which Invited: 4 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis.2012

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

      PLoS One

      Volume: 7 Issue: 12 Pages: e52272-e52272

    • DOI

      10.1371/journal.pone.0052272

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Claudin-4 isinduced in thymocytes of late CD4/CD8 doublepositive stage by E2A and promotes abT cellreceptor.mediated positive selection2011

    • Author(s)
      Kawai. K. Hamazaki, Y., Fujita, H., Fujita,A., Sato, T., Moriwaki, K., Furuse, M., Fujimoto,T., Agata, Y. and Minato, N
    • Journal Title

      Proc. Nat. Acad. Sci. USA

      Volume: 108(10) Issue: 10 Pages: 4075-4080

    • DOI

      10.1073/pnas.1014178108

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spa-1 (Sipa1) controlsthe invasion and metastasis of human prostatecancers via Rap signal2011

    • Author(s)
      Shimizu Y, Hamazaki Y, Hattori M, Doi K,Terada Y, Kobayashi T, Toda Y, Yamasak T,Inoue T, Kajita Y, Atsushi M, Kamba T, MikamiY, Kamoto T, Yamada T, Ogawa O, Minato Nand Nakamura E
    • Journal Title

      Cancer Science

      Volume: 102 Issue: 4 Pages: 828-836

    • DOI

      10.1111/j.1349-7006.2011.01876.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased c-Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency2011

    • Author(s)
      Tanaka H, Tamura A, Sekai M, Hamazaki Y, Minato N
    • Journal Title

      Cancer science

      Volume: 102 Issue: 4 Pages: 784-791

    • DOI

      10.1111/j.1349-7006.2011.01850.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency2011

    • Author(s)
      Kawai Y, Hamazaki Y, Fujita H, Fujita A, Sato T, Furuse M, Fujimoto T, Jetten AM, Agata Y, Minato N
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 108(10) Pages: 4075-80

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SPA-1 controls the invasion and metastasis of human prostate cancer2011

    • Author(s)
      Shimizu Y, Hamazaki Y, Hattori M, Doi K, Terada N, Kobayashi T, Toda Y, Yamasaki T, Inoue T, Kajita Y, Maeno A, Kamba T, Mikami Y, Kamoto T, Yamada T, Kanno T, Yoshikawa K, Ogawa O, Minato N, Nakamura E
    • Journal Title

      Cancer Sci

      Volume: 102(4) Pages: 828-36

    • NAID

      10029292527

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased c-Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency2011

    • Author(s)
      Tanaka H, Tamura A, Sekai M, Hamazaki Y, Minato N.
    • Journal Title

      Cancer Sci

      Volume: 102(4) Pages: 784-91

    • NAID

      10029292347

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis2012

    • Author(s)
      藤田春美、〓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
      マリンメッセ福岡 (福岡県)ショートトーク・ポスター発表
    • Year and Date
      2012-12-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of thymic epithelial stem cells ensuring lifelong central T-cell tolerance2012

    • Author(s)
      Miho Sekai, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県) 口頭発表
    • Year and Date
      2012-12-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Claudin-5 is a Crucial Component of Blood-thymus Barrier by Regulating Vascular Permeability2012

    • Author(s)
      Takahiro Nagatake, Yan-Chun Zhao, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県) 口頭発表
    • Year and Date
      2012-12-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Claudin-5 plays a role in establishing specific thymic microenvironment by regulating vascular permeability.2012

    • Author(s)
      Takahiro Nagatake, Yan-Chun Zhao, Nagahiro Minato and Yoko Hamazaki
    • Organizer
      ThymUS international conference 2012
    • Place of Presentation
      Trump International Beach Resort、マイアミ(アメリカ)
    • Year and Date
      2012-11-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life2012

    • Author(s)
      濱崎洋子
    • Organizer
      RCAI Seminar Series 2011
    • 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(RCAI)(招待講演)
    • Year and Date
      2012-02-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life2012

    • Author(s)
      濱崎洋子
    • Organizer
      特定領域研究(免疫系自己)国際シンポジウム
    • Place of Presentation
      京都大学紫蘭会館(招待講演)
    • Year and Date
      2012-01-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy2011

    • Author(s)
      Kyosuke Sato, Suhail Tahir, Yuji Fukushima, Yasuhiro Nakashima, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      幕張メッセ(千葉) 口頭発表
    • Year and Date
      2011-11-29
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy2011

    • Author(s)
      Kyosuke Sato, Suhail Tahir, Yuji Fukushima, Yasuhiro Nakashima, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      千葉(幕張メッセ)
    • Year and Date
      2011-11-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla2011

    • Author(s)
      Miho Sekai, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      幕張メッセ(千葉) 口頭発表
    • Year and Date
      2011-11-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla2011

    • Author(s)
      Miho Sekai, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      千葉(幕張メッセ)
    • Year and Date
      2011-11-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 加齢に伴い増加する新規CD4 T細胞サブセット(T-sen)の同定とその意義2011

    • Author(s)
      濱崎洋子、湊長博
    • Organizer
      日本食品免疫学会第7回学術総会
    • Place of Presentation
      東京(東京大学安田講堂)(招待講演)
    • Year and Date
      2011-10-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 自己と非自己を見分ける免疫のしくみ2011

    • Author(s)
      濱崎洋子
    • Organizer
      京大サロントーク
    • Place of Presentation
      京大サロン京都(招待講演)
    • Year and Date
      2011-07-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling2011

    • Author(s)
      Harumi Fujita, Yohei Kawai, Akikazu Fujita, Toyoshi Fujimoto, Mikio Furuse, Yasutoshi Agata, Nagahiro Minato and Yoko Hamazaki
    • Organizer
      北海道大学札幌(北海道) 口頭発表
    • Place of Presentation
      第63回日本細胞生物学会大会
    • Year and Date
      2011-06-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling2011

    • Author(s)
      Harumi Fujita, Yohei Kawai, Akikazu Fujita, Toyoshi Fujimoto, Mikio Furuse, Yasutoshi Agata, Nagahiro Minato, Yoko Hamazaki
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      札幌(北海道大学)
    • Year and Date
      2011-06-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy2011

    • Author(s)
      Suhail Tahir, Kyosuke Sato, Yasuhiro Nakashima, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第10回オステオポンチン研究会
    • Place of Presentation
      北海道大学 札幌 (北海道)口頭発表
    • Year and Date
      2011-06-19
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy2011

    • Author(s)
      Suhail Tahir, Kyosuke Sato, Yasuhiro Nakashima, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      第10回オステオポンチン研究会
    • Place of Presentation
      札幌(北海道大学)
    • Year and Date
      2011-06-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] クローディン4はEタンパク質の活性によって後期DP細胞で発現誘導され、ポジティブセレクションの効率化に寄与する2011

    • Author(s)
      河合洋平、濱崎洋子、藤田春美、縣保年、湊長博
    • Organizer
      第21回 Kyoto T cell conference
    • Place of Presentation
      京都平安ホテル 口頭発表
    • Year and Date
      2011-06-10
    • Related Report
      2011 Final Research Report
  • [Presentation] クローディン4はEタンパク質の活性によって後期DP細胞で発現誘導され、ポジティブセレクションの効率化に寄与する2011

    • Author(s)
      河合洋平、濱崎洋子、藤田春美、懸保年、湊長博
    • Organizer
      Kyoto T cell conference
    • Place of Presentation
      京都(京都平安ホテル)
    • Year and Date
      2011-06-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Claudin expression in the thymus and its implication in T-cell development2011

    • Author(s)
      濱崎洋子
    • Organizer
      華中科技大学同済医学院での招待講演
    • Place of Presentation
      華中科技大学同済医学院武漢中華人民共和国(招待講演)
    • Year and Date
      2011-03-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Claudin expression in the thymus and its implication in T-cell development2011

    • Author(s)
      濱崎洋子
    • Organizer
      華中科技大学での招待講演
    • Place of Presentation
      華中科技大学武漢中華人民共和国(招待講演)
    • Year and Date
      2011-03-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 胸腺組織上皮細胞の発生・分化と目己免疫寛容成立機構の解明2011

    • Author(s)
      濱崎洋子
    • Organizer
      京都大学優秀女性研究者賞(たちばな賞)受賞講演
    • Place of Presentation
      京都(京都大学紫蘭会館)(招待講演)
    • Year and Date
      2011-03-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Tight junction-independent expression of claudin-4 in thymic lymphocytes and its role in TCR-signaling2010

    • Author(s)
      Yoko Hamazaki1, Yohei Kawai, Harumi Fujita, Akikazu Fujita, Toyoshi Fujimoto and Nagahiro Minato
    • Organizer
      第62回日本細胞生物学会総会
    • Place of Presentation
      大阪 口頭発表*若手最優秀発表賞
    • Year and Date
      2010-05-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Tight junction-independent expression of claudin-4 in thymic lymphocytes and its role in TCR-signaling2010

    • Author(s)
      Yoko Hamazakil, Yohei Kawai, Harumi Fujita, Akikazu Fujita, Toyoshi Fujimoto, Nagahiro Minato
    • Organizer
      第62回日本細胞生物学会総会
    • Place of Presentation
      大阪(大阪国際会議場)
    • Year and Date
      2010-05-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Claudin-4 expression in thymocytes and its role in T-cell development2010

    • Author(s)
      Yoko Hamazaki, Harumi Fujita, Yohei Kawai and Nagahiro Minato
    • Organizer
      An International workshop on T lymphocytes
    • Place of Presentation
      ThymOZ オーストラリア 口頭発表
    • Year and Date
      2010-03-20
    • Related Report
      2011 Final Research Report
  • [Presentation] The claudin-3,4 positive mTEC progenitors maintain the potential to generate Aire expressing mTECs over fetal stage2010

    • Author(s)
      Miho Sekai, Yoko Hamazaki,Nagahiro Minato
    • Organizer
      European Congress of Immunology Liverpool
    • Place of Presentation
      UK ポスター発表
    • Related Report
      2011 Final Research Report
  • [Presentation] The claudin-3,4 positive mTEC progenitors maintain the potential to generate Aire expressing mTECs over fetal stage2010

    • Author(s)
      Miho Sekai, Yoko Hamazaki, Nagahiro Minato
    • Organizer
      European Congress of Immunology
    • Place of Presentation
      Liverpool, UK
    • Related Report
      2010 Annual Research Report
  • [Presentation] Claudin expression in Thymocytes: Implication in T cell Development2009

    • Author(s)
      Yohei Kawai, Yoko Hamazaki, Harumi Fujita and Nagahiro Minato
    • Organizer
      日本免疫学会
    • Place of Presentation
      大阪 口頭発表
    • Year and Date
      2009-12-02
    • Related Report
      2011 Final Research Report
  • [Presentation] Claudin expression in thymocytes; Implication in T cell development2009

    • Author(s)
      Yoko Hamazaki, Yohei Kawai, Harumi Fujita, Miho Sekai, and Nagahiro Minato
    • Organizer
      The International Workshop on Kyoto T cell Conference
    • Place of Presentation
      京都 ポスター発表
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life

    • Author(s)
      Yoko Hamazaki
    • Organizer
      RCAI Seminar Series 2011
    • 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
      2011 Annual Research Report
    • Invited
  • [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life

    • Author(s)
      Yoko Hamazaki
    • Organizer
      特定領域研究(免疫系自己)国際シンポジウム
    • Place of Presentation
      京都大学 紫蘭会館
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 加齢に伴い増加する新規CD4 T細胞サブセット(T-sen)の同定とその意義

    • Author(s)
      濱崎洋子、湊長博
    • Organizer
      日本食品免疫学会 第7回学術総会
    • Place of Presentation
      東京大学安田講堂 東京
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 自己と非自己を見分ける免疫のしくみ

    • Author(s)
      濱崎洋子
    • Organizer
      京大サロントーク
    • Place of Presentation
      京都大学百周年記念館 京大サロン 京都
    • Related Report
      2011 Annual Research 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
      マリンメッセ福岡    (福岡県)
    • Related Report
      2011 Annual Research 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
      2011 Annual Research 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
      ThymUS international conference 2012
    • Place of Presentation
      神戸国際会議場(兵庫県
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy

    • Author(s)
      Kyosuke Sato, Suhail Tahir, Yuji Fukushima, Yasuhiro Nakashima, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第40回日本免疫学会総会(口頭発表)
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla

    • Author(s)
      Miho Sekai, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第40回日本免疫学会総会(口頭発表)
    • Place of Presentation
      幕張メッセ(千葉)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling.

    • Author(s)
      Harumi Fujita, Yohei Kawai, Akikazu Fujita, Toyoshi Fujimoto, Mikio Furuse, Yasutoshi Agata, Nagahiro Minato and Yoko Hamazaki
    • Organizer
      第63回日本細胞生物学会大会(口頭発表)
    • Place of Presentation
      北海道大学 札幌(北海道)
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy

    • Author(s)
      Suhail Tahir, Kyosuke Sato, Yasuhiro Nakashima, Yoko Hamazaki and Nagahiro Minato
    • Organizer
      第10回オステオポンチン研究会(口頭発表
    • Place of Presentation
      北海道大学 札幌(北海道)
    • Related Report
      2011 Annual Research Report
  • [Presentation] クローディン4はEタンパク質の活性によって後期DP細胞で発現誘導され、ポジティブセレクションの効率化に寄与する

    • Author(s)
      河合洋平、濱崎洋子、藤田春美、縣保年、湊長博
    • Organizer
      第21回Kyoto T cell conference (口頭発表)
    • Place of Presentation
      京都平安ホテル(京都府
    • Related Report
      2011 Annual Research Report
  • [Book] エッセンシャル免疫学 (第2版)2010

    • Author(s)
      監修 笹月健彦
    • Publisher
      南江堂
    • Related Report
      2011 Final Research Report
  • [Book] エッセンシャル免疫学(第2版)2010

    • Author(s)
      監修笹月健彦
    • Total Pages
      552
    • Publisher
      メディカル・サイエンス・インターナショナル
    • Related Report
      2010 Annual Research Report
  • [Book] 免疫生物学第7版2010

    • Author(s)
      監修笹月健彦
    • Total Pages
      870
    • Publisher
      南江堂
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.natureasia.com/japan/jobs/tokushu/detail.php?id=505

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news7/2010/110303_3.htm

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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