Molecular mechanisms underlying formation of lymphatic tissue microenvironment required for preventing autoimmunity

• Project/Area Number: 24390071
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: AKIYAMA TAISHIN 東京大学, 医科学研究所, 准教授 (50327665)
• Co-Investigator(Renkei-kenkyūsha): INOUE Jun-ichiro 東京大学, 医科学研究所, 教授 (70176428)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 自己免疫 / 胸腺 / 制御性T細胞 / 抗原提示細胞 / 癌免疫 / シグナル / リンパ組織 / T細胞 / サイトカインシグナル / 転写因子 / サイトカイン

Outline of Final Research Achievements

Autoimmune diseases are provoked when acquired immune response to self-tissue-derived antigens initiate and continue. Normally, several different mechanisms prevent onsets of autoimmune diseases. Regulatory T cells suppress or attenuate immune responses and thereby play a critical role in preventing autoimmune disease onsets. A large part of regulatory T cells are generated in lymphoid organ thymus. This study identified a molecular mechanisms regulating formation of microenvironment required for generation of regulatory T cells in the thymus. Moreover, involvements of such mechanism in regulation of immune responses to self-tissues and tumors were addressed. This information would provide important insights in medical application of regulator T cells in future.

Research Products

• [Journal Article] Excess NF-kB induces ectopic odontogenesis in embryonic incisor epithelium. (2015)
  • Author(s): Blackburn, J., Kawasaki, K., Porntaveetus, T., Kawasaki, M., Otsuka-Tanaka, Y., Miake, Y., Ota, M.S., Watanabe, M., Hishinuma, M., Nomoto, T., Oommen, S., Ghafoor, S., Harada, F., Nozawa-Inoue, K., Maeda, T., Peterková, R., Lesot, H., Inoue, J., Akiyama, T.,
  • Journal Title: J. Dent. Res Volume: 94 Issue: 1 Pages: 121-128
  • DOI: 10.1177/0022034514556707
  • Peer Reviewed / Open Access
• [Journal Article] Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation. (2014)
  • Author(s): Akiyama, N., Shinzawa, M., Miyauchi, M., Yanai, H., Tateishi, R., Shimo, Y., Ohshima, D., Matsuo, M., Sasaki. I., Hoshino, K., Wu, G., Yagi, S., Inoue, J., Kaisho, T. and Akiyama, T.
  • Journal Title: J. Exp. Med. Volume: 211 Issue: 12 Pages: 2425-2438
  • DOI: 10.1084/jem.20141207
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondria-nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN (2014)
  • Author(s): Akiyama, T., Shiraishi, T., Qin, J., Konno, H., Akiyama, N., Shinzawa, M., Miyauchi, M., Takizawa, N., Yanai, H., Ohashi, H., Miyamoto-Sato, E., Yanagawa, H., Yong, W., Shou, W. and Inoue, J.
  • Journal Title: PLoS ONE Volume: 9(5) Issue: 5 Pages: e95992-e95992
  • DOI: 10.1371/journal.pone.0095992
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of transcription factors activated in thymic epithelial cells during embryonic thymus development. (2014)
  • Author(s): Akiyama, T., Qin, J., Ohshima, D. and Inoue, J.
  • Journal Title: Methods Mol. Biol. Volume: 1164 Pages: 163-170
  • DOI: 10.1007/978-1-4939-0805-9_13
  • ISBN: 9781493908042, 9781493908059
  • Peer Reviewed
• [Journal Article] Regulation of gene expressions in medullary thymic epithelial cells essential for preventing the onset of autoimmune disease (2013)
  • Author(s): Akiyama T et al.
  • Journal Title: Front. Immunol. Volume: 4 Pages: 249-249
  • DOI: 10.3389/fimmu.2013.00249
  • Peer Reviewed
• [Journal Article] Shinzawa M and Akiyama N RANKL-RANK interaction in immune (2012)
  • Author(s): Akiyama T
  • Journal Title: regulatory systems World J. Orthop. Volume: 3 Issue: 9 Pages: 142-150
  • DOI: 10.5312/wjo.v3.i9.142
  • Peer Reviewed
• [Journal Article] TNF receptor family signaling in the development and functions of medullary thymic epithelial cells. (2012)
  • Author(s): Akiyama T
  • Journal Title: Front. Immunol. Volume: 3 Pages: 278-278
  • DOI: 10.3389/fimmu.2012.00278
  • Peer Reviewed
• [Journal Article] DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells (2012)
  • Author(s): Wu G., Hirabayashi K, Sato S., Akiyama N., Akiyama T., Shiota K., and Yagi S
  • Journal Title: BMC Immunol Volume: 13 Issue: 1 Pages: 58-58
  • DOI: 10.1186/1471-2172-13-58
  • Peer Reviewed
• [Presentation] Mitochondria-nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN (2014)
  • Author(s): Taishin Akiyama
  • Organizer: 第43回 日本免疫学会学術集会
  • Place of Presentation: 京都、京都国際会議場
  • Year and Date: 2014-12-11
• [Presentation] T cell-specific CNOT3 depletion alters thymic T cell development and provokes autoimmunity (2014)
  • Author(s): ITOH-KUREHA Taku
  • Organizer: 第43回 日本免疫学会学術集会
  • Place of Presentation: 京都、京都国際会議場
  • Year and Date: 2014-12-10
• [Presentation] 非古典的NF-kB経路の振動による転写制御メカニズムの解析 (2014)
  • Author(s): 関 崇生
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 神戸、神戸国際会議場
  • Year and Date: 2014-11-27
• [Presentation] T細胞特異的CNOT3欠損マウスにおけるT細胞分化・機能異常と自己免疫疾患発症 (2014)
  • Author(s): 呉羽 拓
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 神戸、神戸国際会議場
  • Year and Date: 2014-11-26
• [Presentation] ETSファミリー転写因子Spi-Bは髄質上皮細胞の遺伝子発現を制御する (2014)
  • Author(s): 秋山 泰身
  • Organizer: 京都T細胞会議
  • Place of Presentation: 京都、芝蘭会館
  • Year and Date: 2014-05-16
• [Presentation] 胸腺髄質上皮細胞の分化と機能を制御する分子機構 (2014)
  • Author(s): 秋山 泰身
  • Organizer: 第33回 日本胸腺研究会
  • Place of Presentation: 伊藤国際学術研究センター 東京
  • Invited
• [Presentation] Requirement of RANKL signaling for maintenance of mature mTECs in adult thymus (2013)
  • Author(s): 秋山 泰身ら
  • Organizer: 京都T細胞国際会議
  • Place of Presentation: 芝欄会館 京都
• [Presentation] Roles of lymphotoxin signaling in the development of medullary thymic epithelial cells essential for preventing autoimmunity (2013)
  • Author(s): 滝沢 信和、秋山 泰身ら
  • Organizer: Gradients and Signalling: from chemotaxis to development
  • Place of Presentation: 沖縄科学技術大学院大学 沖縄
• [Presentation] T細胞分化、生存に関与するCNOT3の機能解析 (2013)
  • Author(s): 呉羽 拓、秋山 泰身ら
  • Organizer: 第36回 日本分子生物学会
  • Place of Presentation: 神戸国際会議場 神戸
• [Presentation] Sequential regulation of the development of medullaru thymic epithelial cells by NF-kB amily (2012)
  • Author(s): 秋山泰身
  • Organizer: 第41回目日本免疫学会学術総会
  • Place of Presentation: 神戸國際会議場(神戸市)
  • Year and Date: 2012-12-05
• [Presentation] The negative-feedback regulation of thymic microenvironment required for self-tolerance (2012)
  • Author(s): Taishin Akiyama
  • Organizer: ThymUS 2012
  • Place of Presentation: 米国 マイアミ市
  • Year and Date: 2012-11-07
• [Presentation] Regulatory mechanism of Ets transcriptional factor Spi - B expression in medullary thymicepithelial cells (2012)
  • Author(s): Miho Shinzawa
  • Organizer: ThymUS 2012
  • Place of Presentation: 米国 マイアミ市
  • Year and Date: 2012-11-05
• [Presentation] 胸腺髄質上皮細胞の分化における非古典的NF-kappaB活性化シグナルの役割 (2012)
  • Author(s): 秋山泰身
  • Organizer: 京都T細胞会議
  • Place of Presentation: 芝蘭会館(京都市)
  • Year and Date: 2012-07-06