Functional analysis of the gene responsible for the hereditary type of human autoimmune disease

• Project/Area Number: 22790931
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: The University of Tokushima
• Principal Investigator: NISHIKAWA Yumiko 徳島大学, 疾患酵素学研究センター, 学術研究員 (60448214)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 胸腺 / 自己免疫疾患 / AIRE / 細胞分化 / 遺伝子改変マウス / 自己寛容

Research Abstract

Aire is a gene responsible for the hereditary type of human autoimmune disease. Elucidation of the mechanisms underlying the Aire-deficient autoimmune pathogenesis would contribute to unveiling the pathogenesis of autoimmune disease. In order to know how the Aire establishes the immune tolerance, we constructed the experimental system where we get the information on the cellular dynamics of Aire-expressing cells. Unexpectedly, we found that Aire is expressed by early embryos prior to the thymic organogenesis. Furthermore, we demonstrated that half-life of Aire-expressing cells is about 1 week, which turned out to be much longer than previously thought.

Research Products

• [Journal Article] Rab13 small G protein and Junctional Rab13-binding protein (JRAB) orchestrate actin cytoskeletal organization during epithelial Junctional development (2012)
  • Author(s): Sakane, A., Abdallah, A.A.M., Nakano, K., Honda, K., Ikeda, W., Nishikawa, Y., Matsumoto, M., Matsushita, N., Kitamura. T., and Sasaki, T
  • Journal Title: J. Biol. Chem Volume: 287(51) Issue: 51 Pages: 42455-424680
  • DOI: 10.1074/jbc.m112.383653
  • 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] IL-21-dependent B cell death driven by prostaglandin E2, a product secre ted from follicular dendritic cells (2011)
  • Author(s): Magari, M.Ohmori, H., et al
  • Journal Title: Journal of Immunology Volume: 187 Issue: 8 Pages: 4210-4218
  • DOI: 10.4049/jimmunol.1100934
  • 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, Hirota F, Yano M, Kitajima H, Miyazaki J, Kawamoto H, Mouri Y, Matsumoto M
  • Journal Title: J Exp Med. Volume: 207 Issue: 5 Pages: 963-971
  • DOI: 10.1084/jem.20092144
  • Peer Reviewed
• [Journal Article] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells priorto end-stage terminal differentiation (2010)
  • Author(s): Nishikawa, Y., et al.
  • Journal Title: J.Exp.Med. Volume: Vol.207 Pages: 963-971
  • Peer Reviewed
• [Presentation] Timing-controlled fate-mapping study reveals essential roles of Aire in the maturation program of Aire-expressing cell lineage (2012)
  • Author(s): Nishikawa, Y., Mouri, Y., Nishijima, H, and Matsumoto, M
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸国際会議場(神戸市)
  • Year and Date: 2012-12-05
• [Presentation] Cell-cycle dependent phosphorylation of AIRE protein exogenously expressed in HeLa cells (2012)
  • Author(s): Nishijima, H., et al
  • Organizer: 4th International Conference on Drug Discovery & Therapy
  • Place of Presentation: Dubai, United Arab Emirates
  • Year and Date: 2012-02-13
• [Presentation] Temporal fate-mapping approach reveals a requirement of Aire for the full maturation program of thymic epithelial cells in the medulla (2012)
  • Author(s): Nishikawa, Y., and Matsumoto, M
  • Organizer: International Symposium on Genetic and Epigenetic Control of Cell Fate
  • Place of Presentation: Kyoto Grand Prince Hotel(京都市)
• [Presentation] Temporal fate-mapping approach reveals a requirement of Aire for the full maturation program of thymic epithelial cells in the medulla (2012)
  • Author(s): Nishikawa Y.
  • Organizer: International Symposium on Genetic and Epigenetic Control of Cell Fate
  • Place of Presentation: グランドプリンスホテル京都（京都府）
• [Presentation] Timing-controlled fate-mapping study reveals essential roles of Aire in the maturation program of Aire-expressing cell lineage (2012)
  • Author(s): Nishikawa Y.
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] AIRE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] 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] セミ・ノッタインマウスを用いた時期特異的Aire発現細胞のfate mapping解析 (2011)
  • Author(s): 西川裕美子, 他
  • Organizer: 第21回Kyoto T Cell Conference
  • Place of Presentation: 京都平安ホテル(京都府)
  • Year and Date: 2011-06-10
• [Presentation] Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma (2011)
  • Author(s): Mouri, Y., et al
  • Organizer: 13^<th> International TNF Conference, TNF 2011
  • Place of Presentation: Awaji, Hyogo, Japan
  • Year and Date: 2011-05-16
• [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: 13thInternational TNF Conference, TNF 2011
  • Place of Presentation: Awaji Yumebutai International Conference Center(淡路市)
• [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., et al.
  • 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: 14thInternational Congress of Immunology
  • Place of Presentation: Kobe Portopia Hotel(神戸市)
  • Year and Date: 2010-08-24
• [Presentation] Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes (2010)
  • Author(s): Mouri, Y., et al.
  • 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: 14thInternational Congress of Immunology
  • Place of Presentation: Kobe Portopia Hotel(神戸市)
  • Year and Date: 2010-08-23
• [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells priorto end-stage terminal differentiation (2010)
  • Author(s): Nishikawa, Y., et al.
  • 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 19th International Rheumatology Symposium
  • Place of Presentation: Kobe Portopia Hotel(神戸市)
  • Year and Date: 2010-04-23
• [Presentation] AIRE and autoimmune disease (2010)
  • Author(s): Matsumoto, M., et al.
  • Organizer: The 19^<th> International Rheumatology Symposium
  • Place of Presentation: Kobe Portopia Hotel, Kobe, Japan
  • Year and Date: 2010-04-23
• [Remarks]
  • URL: http://mms1.ier.tokushima-u.ac.jp/article/0017775.html