Function of claudins in Aire-expressing medullary thymic epithelial cells

• Project/Area Number: 22790458
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kyoto 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: ¥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)
• Keywords: T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.

Research Products

• [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
  • Peer Reviewed
• [Journal Article] Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis (2012)
  • Author(s): Fujita H, Hamazaki Y, Noda Y, Oshima M, and Minato N.
  • Journal Title: PLOS ONE Volume: 7
  • Peer Reviewed
• [Journal Article] Claudin-4 isinduced in thymocytes of late CD4/CD8 doublepositive stage by E2A and promotes abT cellreceptor.mediated positive selection (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Spa-1 (Sipa1) controlsthe invasion and metastasis of human prostatecancers via Rap signal (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Increased c-Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency (2011)
  • 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
  • Peer Reviewed
• [Journal Article] SPA-1 controls the invasion and metastasis of human prostate cancer (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Increased c-Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency (2011)
  • Author(s): Tanaka H, Tamura A, Sekai M, Hamazaki Y, Minato N.
  • Journal Title: Cancer Sci Volume: 102(4) Pages: 784-91
  • NAID: 10029292347
  • Peer Reviewed
• [Presentation] Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis (2012)
  • 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
• [Presentation] Identification of thymic epithelial stem cells ensuring lifelong central T-cell tolerance (2012)
  • 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
• [Presentation] Claudin-5 is a Crucial Component of Blood-thymus Barrier by Regulating Vascular Permeability (2012)
  • 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
• [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
• [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life (2012)
  • 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
• [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life (2012)
  • 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
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • 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
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • 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
• [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla (2011)
  • 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
• [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla (2011)
  • 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
• [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
• [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
• [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling (2011)
  • 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
• [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling (2011)
  • 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
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • 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
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • 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
• [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
• [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
• [Presentation] Claudin expression in the thymus and its implication in T-cell development (2011)
  • 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
• [Presentation] Claudin expression in the thymus and its implication in T-cell development (2011)
  • 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
• [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
• [Presentation] Tight junction-independent expression of claudin-4 in thymic lymphocytes and its role in TCR-signaling (2010)
  • 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
• [Presentation] Tight junction-independent expression of claudin-4 in thymic lymphocytes and its role in TCR-signaling (2010)
  • 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
• [Presentation] Claudin-4 expression in thymocytes and its role in T-cell development (2010)
  • 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
• [Presentation] The claudin-3,4 positive mTEC progenitors maintain the potential to generate Aire expressing mTECs over fetal stage (2010)
  • Author(s): Miho Sekai, Yoko Hamazaki,Nagahiro Minato
  • Organizer: European Congress of Immunology Liverpool
  • Place of Presentation: UK ポスター発表
• [Presentation] The claudin-3,4 positive mTEC progenitors maintain the potential to generate Aire expressing mTECs over fetal stage (2010)
  • Author(s): Miho Sekai, Yoko Hamazaki, Nagahiro Minato
  • Organizer: European Congress of Immunology
  • Place of Presentation: Liverpool, UK
• [Presentation] Claudin expression in Thymocytes: Implication in T cell Development (2009)
  • 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
• [Presentation] Claudin expression in thymocytes; Implication in T cell development (2009)
  • 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
• [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）
  • 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
  • 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
  • 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
  • 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）
• [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
• [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
• [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）
• [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）
• [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）
• [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）
• [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
• [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
• [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
• [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
• [Remarks]
  • URL: http://www.natureasia.com/japan/jobs/tokushu/detail.php?id=505
• [Remarks]
  • URL: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news7/2010/110303_3.htm