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自己免疫疾患における病原性の高いTh17細胞の同定

Research Project

Project/Area Number 15F15414
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

高柳 広  東京大学, 大学院医学系研究科(医学部), 教授 (20334229)

Co-Investigator(Kenkyū-buntansha) WIN STEPHANIE  東京大学, 医学(系)研究科(研究院), 外国人特別研究員
Project Period (FY) 2015-11-09 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2017: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2016: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2015: ¥600,000 (Direct Cost: ¥600,000)
Keywords自己免疫疾患 / T細胞
Outline of Annual Research Achievements

自己免疫疾患の病態形成には免疫応答を促進するTh17細胞と抑制するTreg細胞のバランスが疾患進行の鍵となりうる。関節リウマチはもっとも罹患率の高い自己免疫疾患のひとつであり、慢性的な炎症に引き続いて骨破壊がおこる炎症性骨疾患に分類される。申請者らは自己免疫性関節炎の炎症環境下において炎症と骨破壊を惹起する新規Th17細胞サブセットを見出している。新規Th17細胞サブセットは試験管内では滑膜線維芽細胞のRANKL.発現を誘導することで破骨細胞の分化を強力に誘導したが、滑膜線維芽細胞のRANKLの骨破壊の直接的な寄与については生体内での証明はなされていなかった。本研究では滑膜線維芽細胞でRANKL欠損するマウスを関節炎モデル感受性のマウス背景にて新たに作製し、関節炎を誘導すると炎症は最大レベルまで誘導される一方で、関節部位の骨破壊は抑制された。この結果から滑膜線維芽細胞のRANKLは炎症の成立ではなく、炎症局所の骨破壊の誘導に重要であることが分かった。したがって新規Th17細胞はおもに滑膜線維芽細胞のRANKL発現を誘導することで骨破壊に寄与することが考えられた。また歯周炎は関節炎と同様に炎症性骨疾患に分類されるが、歯周炎の骨破壊においても新規Th17細胞が歯根膜細胞と相互作用することで骨破壊を誘導することを見出した。本研究により新規Th17細胞-間葉系細胞-RANKLが関節炎や歯周炎などの炎症性骨疾患の骨破壊の主軸の一つとなることが示された。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (46 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (34 results) (of which Int'l Joint Research: 14 results,  Invited: 30 results) Book (3 results)

  • [Int'l Joint Research] IBMA(オーストリア)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Host defense against oral microbiota by bone-damaging T cells2018

    • Author(s)
      Tsukasaki Masayuki、Komatsu Noriko、Nagashima Kazuki、Nitta Takeshi、Pluemsakunthai Warunee、Shukunami Chisa、Iwakura Yoichiro、Nakashima Tomoki、Okamoto Kazuo、Takayanagi Hiroshi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 701-701

    • DOI

      10.1038/s41467-018-03147-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems2017

    • Author(s)
      Okamoto Kazuo、Nakashima Tomoki、Shinohara Masahiro、Negishi-Koga Takako、Komatsu Noriko、Terashima Asuka、Sawa Shinichiro、Nitta Takeshi、Takayanagi Hiroshi
    • Journal Title

      Physiological Reviews

      Volume: 97 Issue: 4 Pages: 1295-1349

    • DOI

      10.1152/physrev.00036.2016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LOX Fails to Substitute for RANKL in Osteoclastogenesis2017

    • Author(s)
      Tsukasaki M, Hamada K, Okamoto K, Nagashima K, Terashima A, Komatsu N, Win S, Okamura T, Nitta T, Yasuda H, Penninger JM, Takayanagi H
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 32 Issue: 3 Pages: 434-439

    • DOI

      10.1002/jbmr.2990

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Osteoimmunology: the conceptual framework unifying the immune and skeletal systems2017

    • Author(s)
      Kazuo Okamoto, Tomoki Nakashima, Masahiro Shinohara, Takako Negishi-Koga, Noriko Komatsu, Asuka Terashima, Shinichiro Sawa, Takeshi Nitta and Hiroshi Takayanagi
    • Journal Title

      Physiological Reviews

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immune complexes regulate bone metabolism through FcRγ signalling2015

    • Author(s)
      Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu A, Suda T, Sato K, Takai T, Takayanagi H.
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 6637-6637

    • DOI

      10.1038/ncomms7637

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation.2015

    • Author(s)
      Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: - Issue: 6 Pages: 207137-207137

    • DOI

      10.1136/annrheumdis-2014-207137

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] RANKL inhibition prevents autoimmune inflammation in the central nervous system2015

    • Author(s)
      Guerrini M.M, Okamoto K, Komatsu N, Sawa S, Danks L, Penninger J.M, Nakashima T, Takayanagi H.
    • Journal Title

      Immunity

      Volume: 43 Issue: 6 Pages: 1174-1185

    • DOI

      10.1016/j.immuni.2015.10.017

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulatory T cells in Arthritis2015

    • Author(s)
      Komatsu N, Takayanagi H.
    • Journal Title

      Prog Mol Biol Transl Sci

      Volume: 136 Pages: 207-215

    • DOI

      10.1016/bs.pmbts.2015.07.021

    • ISBN
      9780128034156
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Osteoimmunology and autoimmunity2018

    • Author(s)
      Hiroshi Takayanagi
    • Organizer
      Th 7th NIF Winter School on Advanced Immunology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Osteoimmunology and autoimmune diseases2017

    • Author(s)
      高柳広
    • Organizer
      AAI - Immunology 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Interaction between the immune system and bone metabolism2017

    • Author(s)
      Hiroshi Takayanagi
    • Organizer
      13th World Congress on Inflammation
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨免疫学から見た関節リウマチ治療の病態と治療2017

    • Author(s)
      高柳広
    • Organizer
      第45回日本臨床免疫学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Osteoimmunology and autoimmunity2017

    • Author(s)
      Hiroshi Takayanagi
    • Organizer
      ICIS 2017 (第5回国際サイトカイン・インターフェロン学会年会2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanism of negative selection and osteoimmunology2017

    • Author(s)
      高柳広
    • Organizer
      Midwinter Conference 2017 Advances in Immunobiology
    • Place of Presentation
      Sports & Congress Center Seefeld (オーストリア・ゼーフェルト)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism of inflammation-induced bone loss2017

    • Author(s)
      高柳広
    • Organizer
      Chulalongkorn University Seminar
    • Place of Presentation
      Faculty of Dentistry, Chulalongkorn University (タイ・バンコク)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨免疫学と骨関節疾患治療の進歩2017

    • Author(s)
      高柳広
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール (長崎県・長崎市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨免疫学と関節炎治療の進歩2017

    • Author(s)
      高柳広
    • Organizer
      第9回リウマチ膠原病ウィンターセミナー
    • Place of Presentation
      聖路加国際大学アリス・C・セントジョン・メモリアルホール (東京都・中央区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] RANKLシグナルと骨免疫学2016

    • Author(s)
      高柳広
    • Organizer
      Osteoporosis Conference in 山形
    • Place of Presentation
      山形国際ホテル(山形県山形市)
    • Year and Date
      2016-02-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 'Novel findings of Osteoimmunology and osteoporosis2016

    • Author(s)
      高柳広
    • Organizer
      'Moscow International Forum of Bones and Joints Disorders
    • Place of Presentation
      Moscow State University of Medicine and Dentistry(ロシア・モスクワ)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Interaction of bone and the immune system in inflammation and regeneration2016

    • Author(s)
      高柳広
    • Organizer
      6th International Conference on Osteoimmunology
    • Place of Presentation
      Avra Imperial Hotel (ギリシャ・ハニア)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨免疫におけるRANKLの役割2016

    • Author(s)
      高柳広
    • Organizer
      第2回日本骨免疫学会
    • Place of Presentation
      ホテルモントレ沖縄 スパ&リゾート (沖縄県・国頭郡)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Osteonetwork: Crosstalk between bones to other organs2016

    • Author(s)
      高柳広
    • Organizer
      第3回アジア太平洋骨代謝学会議
    • Place of Presentation
      大阪国際会議場 (大阪府・大阪市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨免疫学 オーバービュー2016

    • Author(s)
      高柳広
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場 (大阪府・大阪市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨免疫学基礎研究の進展2016

    • Author(s)
      高柳広
    • Organizer
      第13回日本病理学会カンファレンス
    • Place of Presentation
      神戸市六甲山ホテル (兵庫県・神戸市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨免疫の進歩2016

    • Author(s)
      高柳広
    • Organizer
      第44回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル (東京都・新宿区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 「骨免疫学による自己免疫疾患への挑戦」抗リウマチ薬による破骨細胞抑制作用を含めて2016

    • Author(s)
      高柳広
    • Organizer
      第3回JCRベーシックリサーチカンファレンス
    • Place of Presentation
      富士ソフトアキバホール (東京都・千代田区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] RANKLと骨免疫学2016

    • Author(s)
      高柳広
    • Organizer
      Bone & Immunology Seminar
    • Place of Presentation
      青蓮会館 (京都府・京都市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechanism of central tolerance and osteoimmunology2016

    • Author(s)
      高柳広
    • Organizer
      Chinese Immunology Society (Taiwan) Annual Meeting
    • Place of Presentation
      Chung-San Medical University (台湾・台中)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] RANKLと骨免疫学の新展開2016

    • Author(s)
      高柳広
    • Organizer
      RANKL Research Conference in Chiba
    • Place of Presentation
      京成ホテルミラマーレ (千葉県・千葉市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Osteoimmunology and mechanism of central immune tolerance2016

    • Author(s)
      高柳広
    • Organizer
      Thailand International Conference of Oral Biology 2016
    • Place of Presentation
      Faculty of Dentistry, Chulalongkorn University (タイ・バンコク)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Lysyl oxidase induce osteoclastogenesis via RANKL-dependent pathway.2016

    • Author(s)
      Koki Hamada, Masayuki Tsukasaki, Kazuo Okamoto, Noriko Komatsu, Hiroshi Takayanagi
    • Organizer
      6th International Conference on Osteoimmunology
    • Place of Presentation
      Avra Imperial Hotel (ギリシャ・ハニア)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己免疫性関節炎における免疫系による破骨細胞の分化誘導機構2016

    • Author(s)
      小松紀子、Lynett Danks,中島友紀、高柳広
    • Organizer
      第2回日本骨免疫学会
    • Place of Presentation
      ホテルモントレ沖縄 スパ&リゾート (沖縄県・国頭郡)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Lysyl oxidaseはRANKL非依存的に破骨細胞分化を誘導するか2016

    • Author(s)
      濱田孝樹、塚崎雅之、岡本一男、小松紀子、高柳広
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      第34回日本骨代謝学会学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 関節炎の炎症部位における破骨細胞誘導細胞の検討2016

    • Author(s)
      小松紀子、Lynett Danks,中島友紀、高柳広
    • Organizer
      第3回JCRベーシックリサーチカンファレンス
    • Place of Presentation
      富士ソフトアキバホール (東京都・千代田区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Osteoimmunology and Autodiseases2015

    • Author(s)
      高柳広
    • Organizer
      Institute of Molecular Biotechnology(IMBA)
    • Place of Presentation
      Institute of Molecular Biotechnology(オーストラリア パース
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨免疫学と関節リウマチ治療の進歩2015

    • Author(s)
      高柳広
    • Organizer
      第25回 日本リウマチ学会北海道・東北支部学術集会
    • Place of Presentation
      盛岡市民文化ホール(岩手県盛岡市)
    • Year and Date
      2015-11-14
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Osteoimmunology and the Mechanism of Bone Destruction in Arthritis2015

    • Author(s)
      高柳広
    • Organizer
      2015 Taiwan Rheumatology Forum
    • Place of Presentation
      Chang Yung-Fa Foundation International Center(台湾)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Osteoimmunology and Autoimmunediseases2015

    • Author(s)
      高柳広
    • Organizer
      Hospital for Special Surgery
    • Place of Presentation
      Hospital for special surgery(アメリカ ニューヨーク)
    • Year and Date
      2015-10-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Osteoimmunology and Rheumatologist2015

    • Author(s)
      高柳広
    • Organizer
      The 17th Asia Pacific League of Associations for Rheumatology Congress
    • Place of Presentation
      チェンナイ(インド)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨免疫学の最前線2015

    • Author(s)
      高柳広
    • Organizer
      福岡骨免疫セミナー
    • Place of Presentation
      ホテル日航福岡
    • Year and Date
      2015-09-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 骨免疫におけるRANKLの役割2015

    • Author(s)
      高柳広
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京 港区)
    • Year and Date
      2015-07-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 骨免疫学から見た関節リウマチ治療の進歩2015

    • Author(s)
      高柳広
    • Organizer
      第16回東葛膠原病研究会 (招待講演)
    • Place of Presentation
      ザ・クレストホテル柏
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 医学の医学のあゆみ / 関節炎誘導性の病原性Th17細胞あゆみ / 関節炎誘導性の病原性Th17細胞2016

    • Author(s)
      小松紀子、高柳広
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2016 Annual Research Report
  • [Book] 実験医学増刊号『自己免疫疾患の発症機構と治療』/ 破骨細胞の制御による治療2015

    • Author(s)
      小松紀子、高柳広
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2015 Annual Research Report
  • [Book] Clinical Calcium.25(12):1749-55. (2015)/ 関節リウマチの骨・軟骨病変のメカニズム2015

    • Author(s)
      小松紀子、高柳広
    • Total Pages
      7
    • Publisher
      医薬ジャーナル社
    • Related Report
      2015 Annual Research Report

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Published: 2015-11-26   Modified: 2024-03-26  

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