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Analysis of AIRE-dependent gene-expression network which controls the differentiation of mTECs

Research Project

Project/Area Number 17K08885
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionThe University of Tokushima

Principal Investigator

NISHIJIMA Hitoshi  徳島大学, 先端酵素学研究所(次世代), 助教 (60425410)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsAire / 胸腺上皮細胞 / 負の選択 / 遺伝子発現 / mTEC / RNA-seq / AIRE / 自己免疫疾患 / 1型糖尿病 / Xcr1陽性樹状細胞 / 胸腺髄質上皮細胞 / 免疫学
Outline of Final Research Achievements

The thymus is an important organ for T cells to establish self-tolerance and non-self responsiveness. Aire expressed in thymic medullary epithelial cells (mTECs) plays an important role in the expression of various antigens in mTEC. In addition to Aire knockout mice, we analyzed mTEC gene expression in mice that over-express Aire (huAIRE transgenic mouse, 3xAire knock-in mouse). We identified the factors that down-regulate in mTECs from both Aire knockout mice and Aire overexpressing mice. We analyzed "negative selection" in the model-system which employed OT-II and RIP-OVA transgenic mice, "negative selection" was also impaired in Aire over-expressing mice. We have newly categorized the regulation of gene expression by Aire.

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患原因遺伝子Aireの同定によって自己免疫疾患の原因究明は、分子生物学的にアプローチできる研究分野へと一変した。本研究は胸腺髄質上皮細胞 (mTEC) の遺伝子発現プロファイルがAire欠失時とAire過剰発現時でどのように変化するのかをin vivoにおいて解析した。また、AIRE欠失及び、AIRE過剰発現による胸腺における「負の選択」機構を検討して、Aireで発現する遺伝子群との相関性を解析した。すなわち胸腺における「負の選択」に機能するAireのターゲット因子の絞り込みを行った。この結果は、T細胞の自己と非自己の識別が胸腺で如何に教育されるのかを理解するものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 1 results)

  • [Journal Article] Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms2019

    • Author(s)
      Matsumoto Minoru、Tsuneyama Koichi、Morimoto Junko、Hosomichi Kazuyoshi、Matsumoto Mitsuru、Nishijima Hitoshi
    • Journal Title

      International Immunology

      Volume: 32 Issue: 2 Pages: 117-131

    • DOI

      10.1093/intimm/dxz066

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AIRE - The Autoimmune Regulator2019

    • Author(s)
      Matsumoto Minoru、Nishijima Hitoshi、Morimoto Junko、Tsuneyama Koichi、Matsumoto Mitsuru
    • Journal Title

      eLS

      Volume: 1 Pages: 1-8

    • DOI

      10.1002/9780470015902.a0027281

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aire Controls in Trans the Production of Medullary Thymic Epithelial Cells Expressing Ly-6C/Ly-6G2018

    • Author(s)
      Morimoto Junko、Nishikawa Yumiko、Kakimoto Takumi、Furutani Kohei、Kihara Naoki、Matsumoto Minoru、Tsuneyama Koichi、Kozono Yuko、Kozono Haruo、Hozumi Katsuto、Hosomichi Kazuyoshi、Nishijima Hitoshi、Matsumoto Mitsuru
    • Journal Title

      The Journal of Immunology

      Volume: 201 Issue: 11 Pages: 3244-3257

    • DOI

      10.4049/jimmunol.1800950

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE)2018

    • Author(s)
      Nishijima Hitoshi、Kajimoto Tatsuya、Matsuoka Yoshiki、Mouri Yasuhiro、Morimoto Junko、Matsumoto Minoru、Kawano Hiroshi、Nishioka Yasuhiko、Uehara Hisanori、Izumi Keisuke、Tsuneyama Koichi、Okazaki Il-mi、Okazaki Taku、Hosomichi Kazuyoshi、Shiraki Ayako、Shibutani Makoto、Mitsumori Kunitoshi、Matsumoto Mitsuru
    • Journal Title

      Journal of Autoimmunity

      Volume: 86 Pages: 75-92

    • DOI

      10.1016/j.jaut.2017.09.006

    • NAID

      120006532435

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Aire-dependent establishment of self-tolerance studied by genetically modified mice.2019

    • Author(s)
      Matsumoto Mitsuru, Morimoto Junko, Matsumoto Minoru, Tsuneyama Koichi, Miyazawa Ryuichiro, Nishijima Hitoshi
    • Organizer
      EMBO Workshop ThymE
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aire-dependent establishment of self-tolerance2019

    • Author(s)
      Matsumoto Mitsuru, Morimoto Junko, Matsumoto Minoru, Tsuneyama Koichi, Miyazawa Ryuichiro, Nishijima Hitoshi
    • Organizer
      The 17th International Congress of Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aireを高発現する胸腺髄質上皮細胞の免疫学的機能とトランスクリプトーム解析2019

    • Author(s)
      Nishijima Hitoshi, Sugita Mizuki, Morimoto Junko, Matsumoto Minoru, Matsumoto Mitsuru
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Expression of Ly6C/6G defines a novel subset of medullary thymic epithelial cells2018

    • Author(s)
      Morimoto Junko、Nishikawa Yumiko、Kihara Naoki、Hosomichi Kazuyoshi、Nishijima Hitoshi、Matsumoto Mitsuru
    • Organizer
      Immunology 2018 - AAI Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Manipulation of thymic and peripheral tolerance by AIRE defines distinct tissue-specific autoimmunity2018

    • Author(s)
      Matsumoto Minoru、Nishijima Hitoshi、Morimoto Junko、Tsuneyama Koichi、Matsumoto Mitsuru
    • Organizer
      11th International Congress on Autoimmunity
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胸腺髄質上皮細胞におけるAire発現レベルと組織特異的自己抗原遺伝子発現との関連性に関する検討2018

    • Author(s)
      Nishijima Hitoshi、Morimoto Junko、Matsumoto Minoru、Matsumoto Mitsuru
    • Organizer
      28 Kyoto T cell Conference (KTCC)
    • Related Report
      2018 Research-status Report
  • [Presentation] Distinct tissue-specific immune response revealed by manipulation of thymic and peripheral tolerance by Aire2018

    • Author(s)
      Matsumoto Minoru、Nishijima Hitoshi、Morimoto Junko、Matsumoto Mitsuru
    • Organizer
      1st International Symposium for "Neo-self"
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of the role of thymic APCs and Aire in the production of thymic Tregs2018

    • Author(s)
      Morimoto Junko、Nishijima Hitoshi、Matsumoto Minoru、Matsumoto Mitsuru
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Transcriptomic analysis of medullary thymic epithelial cells with augmented Aire expression2018

    • Author(s)
      Nishijima Hitoshi、Morimoto Junko、Matsumoto Minoru、Matsumoto Mitsuru
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Acquisition of the resistance to autoimmune diabetes by the expression of human AIRE in BM-derived APCs in NOD2018

    • Author(s)
      Matsumoto Minoru、Nishijima Hitoshi、Morimoto Junko、Tsuneyama Koichi、Matsumoto Mitsuru
    • Organizer
      ThymOz8
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel Aire-dependent subset of mTECs with tolerogenic functions is defined by Ly6 family protein expression2018

    • Author(s)
      Matsumoto Mitsuru、Morimoto Junko、Matsumoto Minoru、 Tsuneyama Koichi、Nishijima Hitoshi
    • Organizer
      ThymOz8
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression of Ly6C/6G defines a novel subset of medullary thymic epithelial cells2017

    • Author(s)
      Morimoto Junko、Nishikawa Yumiko、Kihara Naoki、Hosomichi Kazuyoshi、Nishijima Hitoshi、Matsumoto Mitsuru
    • Organizer
      5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transgenic human AIRE expression in NOD acquired resistance to the diabetes due to the impaired presentation of self-antigens in the pancreas2017

    • Author(s)
      Matsumoto Minoru、Nishijima Hitoshi、Morimoto Junko、Tsuneyama Koichi、Matsumoto Mitsuru
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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