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Mimetic virus-infection in thymic medullary microenvironment

Research Project

Project/Area Number 22659094
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

AKIYAMA Taishin  東京大学, 医科学研究所, 准教授 (50327665)

Research Collaborator SHIMO Yusuke  東京大学, 新領域創成科学科, 大学院生
OHSHIMA Daisuke  東京大学, 新領域創成科学科, 大学院生
SHINZAWA Miho  東京大学, 新領域創成科学, 大学院生
秋山 伸子  , 日本学術振興会特別研究員
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,030,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords免疫寛容 / 自己免疫 / 胸腺 / インターフェロン / 炎症 / TNF / 転写因子
Research Abstract

Thymus generates T cells essential for acquired immune responses against pathogens or other foreign antigens. In the thymus, T cells tolerant to self-antigens are selected. Medullary thymic epithelial cells(mTECs) play a critical role of this selection mechanism. Thus, mTECs ectopically express a wide variety of self-antigens that are normally expressed in tissue restricted manner. mTECs present these self-antigens to developing T cells, thereby eliminating the T cells responsive to self-tissues. In this study, we found that proteins induced by virus-infection were ectopically expressed in mTECs. This finding implies the novel link between natural inflammation and self-tolerant mechanism in the thymus.

Report

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

    (44 results)

All 2011 2010 Other

All Journal Article (17 results) (of which Peer Reviewed: 11 results) Presentation (24 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Splenic extramedullary hemopoiesis caused by a dysfunctional mutation inthe2011

    • Author(s)
      Shinzawa M., Maruyama Y., Qin J., Akiyama N., Miyauchi M., Yanai H., Takami M., Inoue J., and Akiyama T*(corresponding author).
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 414 Issue: 4 Pages: 773-778

    • DOI

      10.1016/j.bbrc.2011.10.001

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] RANK signaling induces interferon-stimulated genes inthe fetal thymic2011

    • Author(s)
      Ohshima D., Qin J., Konno H., Hirosawa A., Shiraishi T., Yanai H., Shimo Y., Shinzawa M., Akiyama N., Yamashita R., Nakai K., Akiyama T*(corresponding author), and
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 408 Issue: 4 Pages: 530-536

    • DOI

      10.1016/j.bbrc.2011.04.049

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Okumura K., Kamradt T., Saito H., Nakae S. Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage2011

    • Author(s)
      Ohno T., Oboki K., Kajiwara N., Tanaka S., Ikeda M., Iikura M., Akiyama T., Inoue J., Matsumoto K., Sudo K., Azuma M.,
    • Journal Title

      Plos One

      Volume: 6 Issue: 4 Pages: 18404-18404

    • DOI

      10.1371/journal.pone.0018404

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma2011

    • Author(s)
      Mouri Y
    • Journal Title

      Journal of Immunology

      Volume: 186 Issue: 9 Pages: 5047-5057

    • DOI

      10.4049/jimmunol.1003533

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] TRAF6 directs commitment to regulatory T cells in thymocytes2011

    • Author(s)
      Shimo, Y., et al
    • Journal Title

      Genes to Cells

      Volume: 16 Issue: 4 Pages: 437-447

    • DOI

      10.1111/j.1365-2443.2011.01500.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of central tolerance by RANKL signaling2011

    • Author(s)
      Shinzawa M., and Akiyama T.
    • Journal Title

      Clin Calcium 21.

      Pages: 1193-1199

    • Related Report
      2011 Final Research Report
  • [Journal Article] TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling2011

    • Author(s)
      Motegi H., Shimo Y., Akiyama T. and Inoue
    • Journal Title

      Genes Cells.

      Volume: 16 Issue: 2 Pages: 179-89

    • DOI

      10.1111/j.1365-2443.2010.01474.x

    • Related Report
      2011 Final Research Report
  • [Journal Article] Therapeutic Potential of Anti-Interleukin-17A Aptamer: Suppression of Interleukin-17A signaling and Attenuation of autoimmunity in2011

    • Author(s)
      Ishiguro A, Akiyama T, Inoue J., and
    • Journal Title

      Arth. Rheu

      Volume: 63 Issue: 2 Pages: 455-66

    • DOI

      10.1002/art.30108

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] RANK and CD40 signaling induce expression of AIRE in medullary thymic epithelial cells2011

    • Author(s)
      秋山伸子, ら
    • Journal Title

      Clinical Immunology and Allergology

      Volume: 56 Pages: 238-246

    • NAID

      40019017857

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Regulation of central tolerance by RANKL signaling2011

    • Author(s)
      新澤美穂, ら
    • Journal Title

      Clin Calcium

      Volume: 21 Pages: 1193-1199

    • Related Report
      2011 Annual Research Report
  • [Journal Article] TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling2011

    • Author(s)
      Motegi, et al.
    • Journal Title

      Genes Cell

      Volume: 16 Pages: 179-180

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Potential of Anti-Interleukin-17A Aptamer : Suppression of Interleukin-17A signaling and Attenuation of autoimmunity in mouse models2011

    • Author(s)
      Ishiguro, et al.
    • Journal Title

      Arth.Rheu

      Volume: 63 Pages: 455-466

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Requiem protein links RelB/p52 and the Brm-type SWI/SNF complex in a non-canonical NF-〓B pathway.2010

    • Author(s)
      ando T, Ishizaka A, Watanabe H, Ito T, Iida S, Haraguchi T, Mizutani T, Izumi T, Isobe T, Akiyama T, Inoue J and Iba H.
    • Journal Title

      J. Biol. Chem

      Volume: 285 Issue: 29 Pages: 21951-60

    • DOI

      10.1074/jbc.m109.087783

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human lactoferrin activates NF-kB through Toll-like receptor 4 (TLR4) pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling2010

    • Author(s)
      Ando K, Hasegawa K, Shindo K, Furusawa T, Fujino T, Kikugawa K, Nakano H, Takeuchi O, Akira S, Akiyama T, Gohda J, Inoue J, Hayakawa M.
    • Journal Title

      FEBS J.

      Volume: 277 Issue: 9 Pages: 2051-2066

    • DOI

      10.1111/j.1742-4658.2010.07620.x

    • Related Report
      2011 Final Research Report
  • [Journal Article] Requiem protein links RelB/p52 and the Brm-type SWI/SNF complex in a non-canonical NF-κB pathway2010

    • Author(s)
      Tando, et al.
    • Journal Title

      J.Biol.Chem.

      Volume: 2856 Pages: 21915-21960

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human lactoferrin activates NF-kappaB through the Toll-like receptor 4 pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling2010

    • Author(s)
      Ando, et al.
    • Journal Title

      FEBS lett.

      Volume: 277 Pages: 2051-2066

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 自己免疫寛容を誘導する胸腺内シグナル制御機構2010

    • Author(s)
      新澤, ら
    • Journal Title

      化学と生物

      Volume: 49 Pages: 2-4

    • Related Report
      2010 Annual Research Report
  • [Presentation] Oscillation of non-canonical NF-kB activation pathway2011

    • Author(s)
      関崇生
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜、パシフィコ横浜
    • Year and Date
      2011-12-16
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Molecular mechanisms to establish the thymic microenvironment essential for central tolerance2011

    • Author(s)
      Taishin Akiyama
    • Organizer
      6th Chiba University G-COE Symposium
    • Place of Presentation
      千葉、ホテルニューオータニ幕張
    • Year and Date
      2011-11-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular mechanisms to establish the thymic microenvironment essential for central tolerance2011

    • Author(s)
      Taishin Akiyama
    • Organizer
      6th Chiba University G-COE Symposium
    • Place of Presentation
      千葉、ホテルニューオータニ幕張(招待講演)
    • Year and Date
      2011-11-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel regulatory mechanism of NF-kB inducing kinase(NIK) activation in the immune system2011

    • Author(s)
      新澤美穂
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Roles of TNF family signals in establishing thymic microenvironment2011

    • Author(s)
      秋山伸子
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] A novel regulatory mechanism of NF-kB inducing kinase (NIK) activation in the immune system2011

    • Author(s)
      新澤美穂
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胸腺髄質上皮細胞の遺伝子発現制御機構2011

    • Author(s)
      秋山泰身
    • Organizer
      京都T cell conference
    • Place of Presentation
      京都芝蘭会館
    • Year and Date
      2011-06-10
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Regulation of gene expressions in the development of medullary thymic epithelial cells2011

    • Author(s)
      Taishin Akiyama
    • Organizer
      EUThyme-Rolduc Meeting
    • Place of Presentation
      オランダ、Leeuvenhorst
    • Year and Date
      2011-05-21
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] RANK signaling induces interferon-stimulated genes in the fetal thymic stroma2011

    • Author(s)
      Taishin Akiyama
    • Organizer
      TNF conference 2011
    • Place of Presentation
      淡路島、夢舞台国際会議場
    • Year and Date
      2011-05-16
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Roles of TNF receptor family members on development of thymic microenvironment required for immunological self-tolerance2011

    • Author(s)
      Taishin Akiyama
    • Organizer
      TNF conference 2011
    • Place of Presentation
      淡路島、夢舞台国際会議場
    • Year and Date
      2011-05-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Roles of TNF receptor family members on development of thymic micro environment required for immunological self-tolerance2011

    • Author(s)
      Taishin Akiyama
    • Organizer
      TNF conference 2011
    • Place of Presentation
      淡路島、夢舞台国際会議場
    • Year and Date
      2011-05-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] REGULATION OF GENE EXPRESSIONS IN MEDULLARY THYMIC EPITHELIAL CELLS2010

    • Author(s)
      秋山泰身
    • Organizer
      The Second Workshop of Synthetic Immunology
    • Place of Presentation
      京都芝蘭会館
    • Year and Date
      2010-12-16
    • Related Report
      2011 Final Research Report
  • [Presentation] REGULATION OF GENE EXPRESSIONS IN MEDULLARY THYMIC EPITHELIAL CELLS2010

    • Author(s)
      秋山泰身, ら
    • Organizer
      The Second Workshop of Synthetic Immunology
    • Place of Presentation
      京都
    • Year and Date
      2010-12-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanisms underlying the development of thymic environment essential for immunological self-tolerance2010

    • Author(s)
      秋山泰身
    • Organizer
      第33回日本分子生物学会・第83回生化学会大会
    • Place of Presentation
      神戸神戸ポートピア
    • Year and Date
      2010-12-06
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular mechanisms underlying the development of thymic environment essential for immunological self-tolerance2010

    • Author(s)
      秋山泰身
    • Organizer
      第33回日本分子生物学会・第83回生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] TRAF6 controls commitment to regulatory T-cell lineage and T-cell receptor signals in thymocytes2010

    • Author(s)
      Yusuke Shimo
    • Organizer
      14th International congress in Immunology
    • Place of Presentation
      神戸神戸ポートピ
    • Year and Date
      2010-08-24
    • Related Report
      2011 Final Research Report
  • [Presentation] TRAF6 controls commitment to regulatory T-cell lineage and T-cell receptor signals in thymocytes2010

    • Author(s)
      Yusuke Shimo, ら
    • Organizer
      14th International congress in Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] A negative feedback regulation of medullary thymic epithelial cell development by RANK signal-dependent expression of osteoprotegerin2010

    • Author(s)
      Taishin Akiyama
    • Place of Presentation
      神戸神戸ポートピア
    • Year and Date
      2010-08-23
    • Related Report
      2011 Final Research Report
  • [Presentation] A negative feedback regulation of medullary thymic epithelial cell development by RANK signal-dependent expression of osteoprotegerin2010

    • Author(s)
      Taishin Akiyama, ら
    • Organizer
      14th International congress in Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] RANKL-RANK-OPG system in establishment of immunological tolerance3rd International Conference on Osteoimmunology2010

    • Author(s)
      Taishin Akiyama
    • Place of Presentation
      ギリシャ、サントリーニ
    • Year and Date
      2010-06-24
    • Related Report
      2011 Final Research Report
  • [Presentation] RANKL-RANK-OPG system in establishment of immunological tolerance2010

    • Author(s)
      Taishin Akiyama
    • Organizer
      3rd International Conference on Osteoimmunology
    • Place of Presentation
      ギリシャ、サントリーニ
    • Year and Date
      2010-06-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 胸腺発生型の制御性T細胞分化を制御するTRAF6シグナルの解析2010

    • Author(s)
      下茂佑輔
    • Organizer
      京都T cell conference
    • Place of Presentation
      京都芝蘭会館
    • Year and Date
      2010-06-04
    • Related Report
      2011 Final Research Report
  • [Presentation] 胸腺発生型の制御性T細胞分化を制御するTRAF6シグナルの解析2010

    • Author(s)
      下茂佑輔, ら
    • Organizer
      京都T cell conference
    • Place of Presentation
      京都
    • Year and Date
      2010-06-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Development of thymic niches essential for preventing autoimmunity2010

    • Author(s)
      Taishin Akiyama
    • Organizer
      The 1st International Conference on Frontiers of Regenerative Medicine & Biomedical Science
    • Place of Presentation
      中国、広州
    • Year and Date
      2010-05-14
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Remarks] アウトリーチ活動免疫ふしぎ未来2011実行委員2011年8月21日、日本科学未来館ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/BunshiHatsugan/index.html

    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] RANKLアンタゴニストを含む癌免疫増強2011

    • Inventor(s)
      秋山泰身、箭内洋見、秋山伸子、保田尚孝
    • Industrial Property Rights Holder
      オリエンタル酵母工業
    • Filing Date
      2011-03-31
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] RANKLアンタゴニストを含む癌免疫増強2011

    • Inventor(s)
      秋山泰身, ら
    • Industrial Property Rights Holder
      オリエンタル酵母工業
    • Industrial Property Number
      2011-079167
    • Filing Date
      2011-03-31
    • Related Report
      2010 Annual Research Report

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

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