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

Research Project

Project/Area Number 21390298
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionThe 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 *help
¥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.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (40 results)

All 2012 2011 2010 2009 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (24 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Parkin interacts with Klokinl for mitochondrial import and maintenance of membrane potential2012

    • Author(s)
      Kuroda Y
    • Journal Title

      Human Molecular Genetics

      Volume: Vol.21 Issue: 5 Pages: 991-1003

    • DOI

      10.1093/hmg/ddr530

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking2011

    • 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

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma2011

    • 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

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla2011

    • Author(s)
      Matsumoto, M
    • Journal Title

      Eur. J. Immunol

      Volume: 41 Pages: 12-17

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T cell tolerance2011

    • 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

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma2011

    • Author(s)
      Mouri Y
    • Journal Title

      Journal of Immunology

      Volume: 186 Issue: 9 Pages: 5047-5057

    • DOI

      10.4049/jimmunol.1003533

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking2011

    • Author(s)
      Fukui R
    • Journal Title

      Immunity

      Volume: 35 Issue: 1 Pages: 69-81

    • DOI

      10.1016/j.immuni.2011.05.010

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla2011

    • Author(s)
      Matsumoto, M.
    • Journal Title

      Eur.J.Immunol.

      Volume: Vol.41 Pages: 12-17

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T cell tolerance2011

    • Author(s)
      Wada, N., et al.
    • Journal Title

      J.Invest.Dermatol.

      Volume: Vol.131 Pages: 410-417

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation2010

    • 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

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation2010

    • Author(s)
      Nishikawa, Y, et al.
    • Journal Title

      J.Exp.Med.

      Volume: Vol.207 Pages: 963-971

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of autoimmune regulator(Aire) in the development of the immune system2009

    • Author(s)
      Matsumoto, M
    • Journal Title

      Microbes Infect

      Volume: 11 Pages: 928-934

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of autoimmune regulator (Aire) in the development of the immune system2009

    • Author(s)
      Matsumoto, M.
    • Journal Title

      Microbes Infect. Vol.11

      Pages: 928-934

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Expression of Aite, a gene responsible for autoimmune disease, in ES cells2011

    • Author(s)
      Matsumoto, M., et al
    • Organizer
      Cell Symposia : Stem Cell Programming & Reprogramming
    • Place of Presentation
      Lisbon, Portugal
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self tolerance2011

    • Author(s)
      Matsumoto, M., et al
    • Organizer
      5th Asian Congress on Autoimmunity
    • Place of Presentation
      Suntec City, Singapore
    • Year and Date
      2011-11-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Role of self-antigen expressed by Aire-expressing cells in the negative selection process2011

    • 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
    • Related Report
      2011 Annual Research Report
  • [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self tolerance2011

    • Author(s)
      Matsumoto, M., et al
    • Organizer
      EUThyme-Rolduc Meeting
    • Place of Presentation
      Leeuwenhorst, The Netherlands
    • Year and Date
      2011-05-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Role of Aire in the organization of thymic microenvironment2011

    • 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
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of self-antigen expressed by Aire-expressing cells in the negative selection process2011

    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self tolerance2011

    • Author(s)
      Matsumoto, M., Nishikawa, Y., Mouri, Y., and Nishijima, H
    • Organizer
      EUThyme-Rolduc Meeting
    • Place of Presentation
      NH Conference Center, Leeuwenhorst, The Netherlands
    • Related Report
      2011 Final Research Report
  • [Presentation] Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma2011

    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] Aire-dependent organization of thymic microenvironment for the establishment of self-tolerance2011

    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] Roles of thymic epithelial cells for the establishment of self-tolerance2010

    • 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
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes2010

    • 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
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation2010

    • 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
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] AIRE and autoimmune disease2010

    • 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
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells priorto_end-stage terminal differentiation2010

    • Author(s)
      Matsumoto, M., et al.
    • Organizer
      Thym Oz
    • Place of Presentation
      Rydges, Gladstone, Australia
    • Year and Date
      2010-03-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation2010

    • Author(s)
      Matsumoto, M., Nishikawa, Y., Hirota, F., Yano, M., Kawamoto, H. and Mouri, Y
    • Organizer
      ThymOz VI
    • Place of Presentation
      Gladstone, Australia
    • Related Report
      2011 Final Research Report
  • [Presentation] ire in thymic epithelial cells in the medulla controls developmental process of thymocytes2009

    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] Aire-dependent organization of thymic microenvironment2009

    • 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
    • Related Report
      2011 Final Research Report
  • [Presentation] Aife-depeadent organization of thymic microenvironment2009

    • 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
    • Related Report
      2009 Annual Research Report
  • [Presentation] Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes2009

    • 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
    • Related Report
      2009 Annual Research Report
  • [Presentation] Aire-dependent organization of thymic microenvironment2009

    • 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
    • Related Report
      2009 Annual Research Report
  • [Presentation] Roles of NIK in-thymic epithelial cells for the establishment of central tolerance2009

    • 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
    • Related Report
      2009 Annual Research Report
  • [Presentation] Roles of NIK in thymic epithelial cells for the establishment of central tolerance2009

    • 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
    • Related Report
      2011 Final Research Report
  • [Book] 炎症・再生医学事典 炎症 炎症メディエーターと細胞AIRE2009

    • Author(s)
      松本満
    • Total Pages
      2
    • Publisher
      朝倉書店
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.tokushima-u.ac.jp/ier/autoimmunity/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://mms1.ier.tokushima-u.ac.jp/article/0017775.html

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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