Studies on the functian of AIRE, a gene responsible for the hereditary type of autoimmune disease

• Project/Area Number: 19390274
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUMOTO MITSURU The University of Tokushima, 疾患酵素学観究センター, 教授 (60221595)
• Co-Investigator(Kenkyū-buntansha): HORIKE Shinichi 徳島大学, 疾患酵素学研究センター, 助教 (40448311) ; HORIKE Makiko 徳島大学, 疾患酵素学研究センター, COE研究員 (20304222)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: 自己免疫疾患 / 胸腺 / AIRE / 自己寛容 / MHC / ノックインマウス

Research Abstract

種々の自己免疫疾患は胸腺における自己寛容成立機構の破綻によって起こると考えられる。自己寛容成立機構における胸腺上皮細胞の役割を胸腺五皮細胞に特異的に発現する転写調節因子AIREの遺伝子改変マウスを用いて解析した。すなわち、AIRE欠損マウス(AIRE-KO)に加え新たにAIRF, 遺伝子の発現制御下に蛍光分子マーカーGFPを発現するATRE/GFPノックインマウス(AIRE/GFP-KI)を作製し、胸腺上皮細胞の分化プログラムにおけるAIREの役割を解析した。その結果、AIREは胸腺上皮細胞が最終分化段階に成熟するために必要な分化因子として作用していることが明らかになった。すなわち、AIRSは多様な自己抗原が発現できる最終分化段階にまで胸腺上皮細胞を分化させるために必要であり、それによって自己寛容の成立に必要となる胸腺微小環境形成に寄与することが示唆された。

Research Products

• [Journal Article] Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology (2008)
  • Author(s): Matsumoto, M., Zhou, Y., Matsuo, S., Nakanishi, H., Hirose, K., Oura, H., Arase, S., Ishida-Yamamoto, A., Bando, Y., Izumi, K., Kiyonari, H., Oshima, N., Nakayama, R., Matsushima, A., Hirota, F., Mouri, Y., Kuroda, N., Sano, S., and Chaplin, D.D.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 6720-6724
• [Journal Article] The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator (2008)
  • Author(s): Hikosaka, Y., Nitta, T., Ohigashi, I., Yana, K., Ishimaru, N., Hayashi, Y., Matsumoto, M., Matsuo, K., Penninger, J.M., Takayanagi, H., Yokota, Y., Yamada, H., Yoshikai, Y., Inoue, J-I., Akiyama, T., and Takahama, Y.
  • Journal Title: Immunity 29 Pages: 438-450
• [Journal Article] The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance (2008)
  • Author(s): Akiyama, T., Shimo, Y., Yanai, H., Qin, J., Ohshima, D., Maruyama, Y., Asaumi, Y., Kitazawa, J., Takayanagi, H., Penninger, J.M., Matsumoto, M., Nitta, T., Takahama, Y., and Inoue, J-I.
  • Journal Title: Immunity 29 Pages: 423-437
• [Journal Article] Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance (2008)
  • Author(s): Yano, M., Kuroda, N., Han, H., Horike, M., Nishikawa, Y., Kiyonari, H., Maemura, K., Yanagawa, Y., Obata, K., Takahashi, S., Ikawa, T., Satoh, R., Kawamoto, H., Mouri, Y., and Matsumoto, M.
  • Journal Title: J. Exp. Med. 205 Pages: 2827-2838
  • NAID: 40016843480
• [Journal Article] Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance. (2008)
  • Author(s): Yano, M., et al.
  • Journal Title: J. Exp. Med. 205 Pages: 2827-2838
  • Peer Reviewed
• [Journal Article] The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. (2008)
  • Author(s): Akiyama, T., et al.
  • Journal Title: Immunity 29 Pages: 423-437
  • Peer Reviewed
• [Journal Article] The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. (2008)
  • Author(s): Hikosaka, Y., et al.
  • Journal Title: Immunity 29 Pages: 438-450
  • Peer Reviewed
• [Journal Article] utoimmune regulator functions in autoimmunity control (2007)
  • Author(s): Matsumoto, M.
  • Journal Title: Expert Rev. Clin. Immunol. 3 Pages: 891-900
• [Journal Article] Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance (2007)
  • Author(s): Matsumoto, M.
  • Journal Title: Arch. Immunol.Ther. Exp. 55 Pages: 27-34
• [Journal Article] N. Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin (2007)
  • Author(s): Hamazaki, Y., Fujita, H., Kobayashi, T., Choi, Y., Scott, H.S., Matsumoto, M., and Minato,
  • Journal Title: Nature Immunol 8 Pages: 304-311
• [Journal Article] Medullary Thymic epithelial cells expressing Aire represent a unique lineage derived from claudin-expressing cells (2007)
  • Author(s): Hamazaki Y., et. al.
  • Journal Title: Nature Immunology 8 Pages: 304-311
  • Peer Reviewed
• [Journal Article] Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance (2007)
  • Author(s): Matsumoto M.
  • Journal Title: Arch.Immunol.Ther.Exp 55 Pages: 27-34
  • Peer Reviewed
• [Journal Article] Autoimmune regulator functions in sutoimmunity control (2007)
  • Author(s): Matsumoto M.
  • Journal Title: Expert Rev.Clin.Immunol 3 Pages: 891-900
  • Peer Reviewed
• [Presentation] Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance (2008)
  • Author(s): CD Masashi, Y., Mouri, Y., Nishikawa, Y., Ikawa, T., Satoh, R., Kawamoto, H., and Matsumoto M.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都(学術集会記録第38巻, p235, 2008.)
  • Year and Date: 2008-12-03
• [Presentation] M. Aire-dependent organization of thymic microenvironment (2008)
  • Author(s): Matsumoto
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都(日本免疫学会総会・学術集会記録第38巻, p8, 2008.)
  • Year and Date: 2008-12-02
• [Presentation] Aire controls the differentiation program of medullary thymic epithelial cells (2008)
  • Author(s): Yano, M., Nishikawa, Y., Ikawa, T., Satoh, R., Kawamoto, H., Mouri, Y.and Matsumoto, M.
  • Organizer: ThymUS San Juan, Puerto Rico
  • Place of Presentation: Abstract(p43)
  • Year and Date: 2008-11-10
• [Presentation] Aire controls the differentiation program of medullary thymic epithelial cells. (2008)
  • Author(s): Yano, M., et al.
  • Organizer: ThymUS
  • Place of Presentation: Puerto Rico
  • Year and Date: 2008-11-10
• [Presentation] D.D. Targeted deletion of the murine corneodesrnosin gene delineates its essential role in skin and hair physiology (2008)
  • Author(s): Matsumoto, M., Sano, S., Ishida-Yamamoto, A., Zhou, Y., Matsuo, S., Nakanishi, H., Hirose, K., Oura, H., Arase, S., and Chaplin
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: Kyoto
  • Year and Date: 2008-05-17
• [Presentation] Target-organ specificity of autoimmunity defined by Aire (2007)
  • Author(s): Niki, S., Mouri, Y., and Matsumoto, M.
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 品川
  • Year and Date: 2007-11-22
• [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self-tolerance (2007)
  • Author(s): Matsumoto, M.
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 品川
  • Year and Date: 2007-11-21
• [Presentation] Transcriptional regulation in the thymus for the establishment of self-tolerance 13<th> International Congress of Immunology Rio de Janeiro (2007)
  • Author(s): Matsumoto, M.
  • Place of Presentation: Brazil
  • Year and Date: 2007-08-21
• [Presentation] Transcriptional regulation in the thymus for the establishment of self-tolerance (2007)
  • Author(s): Matsumoto M.
  • Organizer: 13^<th> International Congress of Immunology
  • Place of Presentation: Rio de Janeiro
  • Year and Date: 2007-08-21
• [Presentation] Thymic stromal factors that regulate establishment and maintenance of self-tolerance RCAI-JSI international Symposium on Immunology 2007 Development and Maintenance of Immune System Pacifico Yokohama (2007)
  • Author(s): Matsumoto, M.
  • Place of Presentation: Yokohama
  • Year and Date: 2007-07-26
• [Presentation] Thymic organogenesis controlled by NF-KB activating factors FOCiS 2007 San Diego (2007)
  • Author(s): Yano, M., Mouri, Y. and Matsumoto, M.
  • Place of Presentation: USA
  • Year and Date: 2007-06-09
• [Presentation] Aire in thymic stroma controls early thymopoiesis The Rolduc Workshop on Thymocyte and T cell Biology Kerkrade (2007)
  • Author(s): Mouri, Y. and Matsumoto, M.
  • Place of Presentation: Netherlands
  • Year and Date: 2007-05-20