Mimetic virus-infection in thymic medullary microenvironment

2011 Fiscal Year Final Research Report

• Project/Area Number: 22659094
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The 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
• Keywords: 免疫寛容 / 自己免疫

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.

Research Products

• [Journal Article] Splenic extramedullary hemopoiesis caused by a dysfunctional mutation in the NF-kB-inducing kinase gene (2011)
  • Author(s): Shinzawa M., Maruyama Y., Qin J., Akiyama N., Miyauchi M., Yanai H., Takami M., Inoue J., and Akiyama T
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 414 Pages: 773-778
  • DOI: DOI:10.1016/j.bbrc.2011.10.001
• [Journal Article] RANK signaling induces interferon-stimulated genes in the fetal thymic stroma (2011)
  • 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, and Inoue J.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 408 Pages: 530-536
  • DOI: DOI:10.1016/j.bbrc.2011.04.049
• [Journal Article] Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation (2011)
  • Author(s): Ohno T., Oboki K., Kajiwara N., Tanaka S., Ikeda M., Iikura M., Akiyama T., Inoue J., Matsumoto K., Sudo K., Azuma M., Okumura K., Kamradt T., Saito H., Nakae S.
  • Journal Title: Plos One Volume: 6 Pages: e18404
  • DOI: DOI:10.1371/journal.pone.0018404
• [Journal Article] Lymphotoxin Signal Promotes Thymic Organogenesis by Eliciting RANK Expression in the Embryonic Thymic Stroma (2011)
  • Author(s): Mouri Y., Yano M., Shinzawa M., Shimo Y., Hirota F., Nishikawa Y, Nii T., Kiyonari H., Abe T., Uehara H., Izumi K., Tamada K., Chen L., Penninger JM., Inoue J., Akiyama T, and Matsumoto M.
  • Journal Title: J. Immunol. Volume: 186 Pages: 5047-57
  • DOI: DOI:10.4049/jimmunol.1003533
• [Journal Article] TRAF6 directs commitment to regulatory T cells in thymocytes (2011)
  • Author(s): Shimo Y., Yanai H., Ohshima D., Qin J., Motegi H., Maruyama Y., Hori S., Inoue J., and Akiyama T
  • Journal Title: Genes Cells Volume: 16 Pages: 437-447
  • DOI: DOI:10.1111/j.1365-2443.2011.01500.x
• [Journal Article] Regulation of central tolerance by RANKL signaling (2011)
  • Author(s): Shinzawa M., and Akiyama T.
  • Journal Title: Clin Calcium 21. Pages: 1193-1199
  • DOI: DOI:CliCa110811931199
• [Journal Article] TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling (2011)
  • Author(s): Motegi H., Shimo Y., Akiyama T. and Inoue J.
  • Journal Title: Genes Cells. Volume: 16 Pages: 179-89
  • DOI: DOI:10.1111/j.1365-2443.2010.01474.x
• [Journal Article] Therapeutic Potential of Anti-Interleukin-17A Aptamer : Suppression of Interleukin-17A signaling and Attenuation of autoimmunity in mouse models. (2011)
  • Author(s): Ishiguro A, Akiyama T, Inoue J., and Nakamura Y
  • Journal Title: Arth. Rheu Volume: 63 Pages: 455-66
  • DOI: DOI:10.1002/art.30108
• [Journal Article] Requiem protein links RelB/p52 and the Brm-type SWI/SNF complex in a non-canonical NF-・B pathway (2010)
  • Author(s): Tando 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 Pages: 21951-60
  • DOI: DOI:10.1074/jbc.M109.087783
• [Journal Article] Human lactoferrin activates NF-kB through Toll-like receptor 4(TLR4) pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling (2010)
  • 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 Pages: 2051-2066
  • DOI: DOI:10.1111/j.1742-4658.2010.07620.x
• [Presentation] Oscillation of non-canonical NF-kB activation pathway (2011)
  • 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
• [Presentation] Molecular mechanisms to establish the thymic microenvironment essential for central tolerance (2011)
  • 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
• [Presentation] A novel regulatory mechanism of NF-kB inducing kinase(NIK) activation in the immune system (2011)
  • 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
• [Presentation] Roles of TNF family signals in establishing thymic microenvironment (2011)
  • 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
• [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
• [Presentation] Regulation of gene expressions in the development of medullary thymic epithelial cells (2011)
  • Author(s): Taishin Akiyama
  • Organizer: EUThyme-Rolduc Meeting
  • Place of Presentation: オランダ、Leeuvenhorst
  • Year and Date: 2011-05-21
• [Presentation] RANK signaling induces interferon-stimulated genes in the fetal thymic stroma (2011)
  • 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
• [Presentation] Roles of TNF receptor family members on development of thymic microenvironment required for immunological self-tolerance (2011)
  • 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
• [Presentation] REGULATION OF GENE EXPRESSIONS IN MEDULLARY THYMIC EPITHELIAL CELLS (2010)
  • 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
• [Presentation] Molecular mechanisms underlying the development of thymic environment essential for immunological self-tolerance (2010)
  • 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
• [Presentation] TRAF6 controls commitment to regulatory T-cell lineage and T-cell receptor signals in thymocytes (2010)
  • 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
• [Presentation] A negative feedback regulation of medullary thymic epithelial cell development by RANK signal-dependent expression of osteoprotegerin (2010)
  • Author(s): Taishin Akiyama
  • Place of Presentation: 神戸神戸ポートピア
  • Year and Date: 2010-08-23
• [Presentation] RANKL-RANK-OPG system in establishment of immunological tolerance3rd International Conference on Osteoimmunology (2010)
  • Author(s): Taishin Akiyama
  • Place of Presentation: ギリシャ、サントリーニ
  • Year and Date: 2010-06-24
• [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
• [Presentation] Development of thymic niches essential for preventing autoimmunity (2010)
  • 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
• [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
• [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
  • Industrial Property Number: 特許、2011-079167
  • Filing Date: 2011-03-31