Transgenic mouse approaches to the pathogenesis of hereditary type of human autoimmune disease

• Project/Area Number: 21390298
• 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 徳島大学, 疾患酵素学研究センター, 教授 (60221595)
• Co-Investigator(Kenkyū-buntansha): NISHIKAWA Yumiko 徳島大学, 疾患酵素学研究センター, 助教 (60448214) ; MOURI Yasuhiro 徳島大学, 疾患酵素学研究センター, 助教 (80464353)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 自己免疫疾患 / 胸腺 / AIRE / 自己寛容 / 胸線

Research Abstract

We sought to monitor the production and maintenance of Aire-expressing medullary thymic epithelial cells(mTECs) by a fate-mapping strategy in which bacterial artificial chromosome transgenic mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. With the use of one transgenic line in which Cre recombinase expression was confined to mTECs, we found that Aire^+ CD80^<high> mTECs further progressed to an Aire^-CD80^<intermediate> stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation.

Research Products

• [Journal Article] Parkin interacts with Klokinl for mitochondrial import and maintenance of membrane potential (2012)
  • Author(s): Kuroda Y
  • Journal Title: Human Molecular Genetics Volume: Vol.21 Issue: 5 Pages: 991-1003
  • DOI: 10.1093/hmg/ddr530
  • Peer Reviewed
• [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking (2011)
  • Author(s): Fukui, R., Saitoh, S.-I., Kanno, A., Onji, M., Shibata, T., Ito, A., Onji, M., Matsumoto, M., Akira, S., Yoshida, N., and Miyake, K
  • Journal Title: Immunity Volume: 35 Pages: 69-81
  • Peer Reviewed
• [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, J. M., Inoue, J., Akiyama, T., and Matsumoto, M
  • Journal Title: J. Immunol Volume: 186 Pages: 5047-5057
  • Peer Reviewed
• [Journal Article] Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla (2011)
  • Author(s): Matsumoto, M
  • Journal Title: Eur. J. Immunol Volume: 41 Pages: 12-17
  • Peer Reviewed
• [Journal Article] Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T cell tolerance (2011)
  • Author(s): Wada, N., Nishifuji, K., Yamada, T., Kudoh, J., Shimizu, N., Matsumoto, M., Peltonen, L., Nagafuchi, S., and Amagai, M
  • Journal Title: J. Invest. Dermatol Volume: 131 Pages: 410-417
  • Peer Reviewed
• [Journal Article] Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma (2011)
  • Author(s): Mouri Y
  • Journal Title: Journal of Immunology Volume: 186 Issue: 9 Pages: 5047-5057
  • DOI: 10.4049/jimmunol.1003533
  • Peer Reviewed
• [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking (2011)
  • Author(s): Fukui R
  • Journal Title: Immunity Volume: 35 Issue: 1 Pages: 69-81
  • DOI: 10.1016/j.immuni.2011.05.010
  • Peer Reviewed
• [Journal Article] Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla (2011)
  • Author(s): Matsumoto, M.
  • Journal Title: Eur.J.Immunol. Volume: Vol.41 Pages: 12-17
  • Peer Reviewed
• [Journal Article] Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T cell tolerance (2011)
  • Author(s): Wada, N., et al.
  • Journal Title: J.Invest.Dermatol. Volume: Vol.131 Pages: 410-417
  • Peer Reviewed
• [Journal Article] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation (2010)
  • Author(s): Nishikawa, Y., Hirota, F., Yano, M., Kitajima, H., Miyazaki, J-i., Kawamoto, H., Mouri, Y., and Matsumoto, M
  • Journal Title: J. Exp. Med Volume: 207 Pages: 963-971
  • NAID: 120004898443
  • Peer Reviewed
• [Journal Article] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation (2010)
  • Author(s): Nishikawa, Y, et al.
  • Journal Title: J.Exp.Med. Volume: Vol.207 Pages: 963-971
  • Peer Reviewed
• [Journal Article] The role of autoimmune regulator(Aire) in the development of the immune system (2009)
  • Author(s): Matsumoto, M
  • Journal Title: Microbes Infect Volume: 11 Pages: 928-934
  • Peer Reviewed
• [Journal Article] The role of autoimmune regulator (Aire) in the development of the immune system (2009)
  • Author(s): Matsumoto, M.
  • Journal Title: Microbes Infect. Vol.11 Pages: 928-934
  • Peer Reviewed
• [Presentation] Expression of Aite, a gene responsible for autoimmune disease, in ES cells (2011)
  • Author(s): Matsumoto, M., et al
  • Organizer: Cell Symposia : Stem Cell Programming & Reprogramming
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2011-12-09
• [Presentation] IRE遺伝子を導入したHeLa細胞における細胞周期依存的なAIREタンパク質のリン酸化 (2011)
  • Author(s): 西嶋仁、毛利安宏、西川裕美子、松本満
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2011-11-27
• [Presentation] Negative selectionにおけるAire発現細胞由来自己抗原の役割 (2011)
  • Author(s): 毛利安宏、西川裕美子、西嶋仁、松本満
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 2011-11-27
• [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self tolerance (2011)
  • Author(s): Matsumoto, M., et al
  • Organizer: 5th Asian Congress on Autoimmunity
  • Place of Presentation: Suntec City, Singapore
  • Year and Date: 2011-11-19
• [Presentation] Role of self-antigen expressed by Aire-expressing cells in the negative selection process (2011)
  • Author(s): Matsumoto, M., et al
  • Organizer: 5th International Conference on Autoimmunity : Mechanisms and Novel Treatments
  • Place of Presentation: Crete, Greece
  • Year and Date: 2011-09-24
• [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self tolerance (2011)
  • Author(s): Matsumoto, M., et al
  • Organizer: EUThyme-Rolduc Meeting
  • Place of Presentation: Leeuwenhorst, The Netherlands
  • Year and Date: 2011-05-22
• [Presentation] Role of Aire in the organization of thymic microenvironment (2011)
  • Author(s): Matsumoto, M., et al.
  • Organizer: Controversies in Rheumatology and Autoimmunity (CORA 2011)
  • Place of Presentation: Firenze Fiera, Florence, Italy
  • Year and Date: 2011-03-10
• [Presentation] Role of self-antigen expressed by Aire-expressing cells in the negative selection process (2011)
  • Author(s): Matsumoto, M., Mouri, Y., Nishikawa, Y., and Nishijima, H
  • Organizer: 5th International Conference on Autoimmunity : Mechanisms and Novel Treatments
  • Place of Presentation: Knossos Royal Village Conference Center, Hersonissos, Crete, Greece
• [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self tolerance (2011)
  • Author(s): Matsumoto, M., Nishikawa, Y., Mouri, Y., and Nishijima, H
  • Organizer: EUThyme-Rolduc Meeting
  • Place of Presentation: NH Conference Center, Leeuwenhorst, The Netherlands
• [Presentation] 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., Nishikawa, Y., Tamada, K., Chen, L., Penninger, J. M., Inoue, J., Akiyama, T., and Matsumoto, M
  • Organizer: 13^<th> International TNF Conference, TNF
  • Place of Presentation: Awaji Yumebutai International Conference Center, Hyogo, Japan
• [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self-tolerance (2011)
  • Author(s): Nishikawa, Y., Mouri, Y., Nishijima, H., and Matsumoto, M
  • Organizer: ESF-JSPS Frontier Science Conference Series for Young Researchers「Cutting Edge Immunology and its Clinical Application」
  • Place of Presentation: Apollo Hotel de Beyaerd, Hulshort, The Netherlands
• [Presentation] Roles of thymic epithelial cells for the establishment of self-tolerance (2010)
  • Author(s): Matsumoto, M
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe Portopia Hotel, Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes (2010)
  • Author(s): Mouri, Y., Nishikawa, Y., and Matsumoto, M
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe Portopia Hotel, Kobe, Japan
  • Year and Date: 2010-08-24
• [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation (2010)
  • Author(s): Nishikawa, Y., Mouri, Y., and Matsumoto, M
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe Portopia Hotel, Kobe, Japan
  • Year and Date: 2010-08-23
• [Presentation] AIRE and autoimmune disease (2010)
  • Author(s): Matsumoto, M., Nishikawa, Y., Hirota, F. and Mouri, Y
  • Organizer: The 19^<th> International Rheumatology Symposium
  • Place of Presentation: Kobe Portopia Hotel, Kobe, Japan
  • Year and Date: 2010-04-23
• [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells priorto_end-stage terminal differentiation (2010)
  • Author(s): Matsumoto, M., et al.
  • Organizer: Thym Oz
  • Place of Presentation: Rydges, Gladstone, Australia
  • Year and Date: 2010-03-19
• [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation (2010)
  • Author(s): Matsumoto, M., Nishikawa, Y., Hirota, F., Yano, M., Kawamoto, H. and Mouri, Y
  • Organizer: ThymOz VI
  • Place of Presentation: Gladstone, Australia
• [Presentation] ire in thymic epithelial cells in the medulla controls developmental process of thymocytes (2009)
  • Author(s): Mouri, Y., and Matsumoto, M
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2009-12-02
• [Presentation] Aire-dependent organization of thymic microenvironment (2009)
  • Author(s): Matsumoto, M
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2009-12-02
• [Presentation] Aife-depeadent organization of thymic microenvironment (2009)
  • Author(s): Matsumoto, M.
  • Organizer: 第39向日本免疫学会総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes (2009)
  • Author(s): Mouri, Y., et at.
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪国際会議掲(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Aire-dependent organization of thymic microenvironment (2009)
  • Author(s): Matsumoto, M., et al.
  • Organizer: 国際KTCC 2009
  • Place of Presentation: 京大芝蘭会館(京郁)
  • Year and Date: 2009-06-03
• [Presentation] Roles of NIK in-thymic epithelial cells for the establishment of central tolerance (2009)
  • Author(s): Mowi, Y., et al.
  • Organizer: 12^<th> International TNF Conference
  • Place of Presentation: San Lotenzo de E1 Escorial, Madrid. Spain
  • Year and Date: 2009-04-26
• [Presentation] Roles of NIK in thymic epithelial cells for the establishment of central tolerance (2009)
  • Author(s): Mouri, Y., Yano, M., and Matsumoto, M
  • Organizer: 12^<th> International TNF Conference
  • Place of Presentation: San Lorenzo de El Escorial, Madrid, Spain
• [Book] 炎症・再生医学事典 炎症 炎症メディエーターと細胞AIRE (2009)
  • Author(s): 松本満
  • Total Pages: 2
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://www.tokushima-u.ac.jp/ier/autoimmunity/
• [Remarks]
  • URL: http://mms1.ier.tokushima-u.ac.jp/article/0017775.html