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紫外線で誘導されるネオ・セルフと制御性T細胞による自己免疫治療法の開発

Publicly Offered Research

Project AreaCreation, function and structure of neo-self
Project/Area Number 17H05798
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNagoya City University

Principal Investigator

山崎 小百合  名古屋市立大学, 大学院医学研究科, 教授 (70567255)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
KeywordsUVB / 制御性T細胞 / 樹状細胞 / 皮膚 / 紫外線
Outline of Annual Research Achievements

研究代表者らは、制御性T細胞が紫外線照射にて皮膚のCD4+T細胞の約60%にも増えることを見出した。制御性T細胞は、通常は末梢CD4+T細胞の5-10%を占め、自己免疫疾患の発症を抑制している重要な免疫担当細胞である。将来、紫外線で増える制御性T細胞を利用した新しい自己免疫疾患の治療法に貢献することを目指し、本研究を遂行した。制御性T細胞は、紫外線により皮膚からレリースされた自己抗原を「ネオ・セルフ」として提示する樹状細胞から抗原提示されて増殖し、自己免疫疾患の発症を抑制していると仮定し、これを証明するために研究を行った。その結果、本公募研究期間の成果として、紫外線で誘導されたネオ・セルフの抗原提示を制御性T細胞に行っている皮膚の樹状細胞サブセットを同定できた(Yamazaki S*et al. J Immunol 2018 *Corresponding author)。この皮膚の樹状細胞サブセットは、従来信じられていた表皮ランゲルハンス細胞とは異なるサブセットであった。さらに、紫外線でネオ・セルフの抗原提示を行う皮膚樹状細胞サブセットにユニークな遺伝子発現プロファイルも発見することができた。これらの発見は、15th International Workshop on Langerhans Cells、International Investigative Dermatology2018、Japan Singapore Skin Research Conference 2019で口演に選ばれ、国際的にも注目されている。現在解析を継続しており、紫外線で誘導されたネオ・セルフと制御性T細胞による新たな治療戦略の基盤となる成果を得ることができた。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (26 results)

All 2019 2018 2017 Other

All Int'l Joint Research (6 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (10 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (2 results)

  • [Int'l Joint Research] Guido Felrazzo/University of Messina(イタリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Su I-hsin/Nanyang Technological University(シンガポール)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Mikael Karlsson/Karolinska Institute(スウェーデン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Michel Nussenzweig/Rockefeller University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Dieter Riethmacher/Nazarbayev University(カザフスタン)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] NAZARBAYEV UNIVERSITY(カザフスタン)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Hyperglycemia is associated with psoriatic inflammation in both humans and mice2019

    • Author(s)
      Ikumi K, Odanaka M, Shime H, Imai M, Osaga S, Taguchi O, Nishida E, Hemmi H, Kaisho T, Morita A, Yamazaki S
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 印刷中 Issue: 6 Pages: 1329-1338

    • DOI

      10.1016/j.jid.2019.01.029

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulatory T cells expressing abundant CTLA-4 on the cell surface with a proliferative gene profile are key features of human head and neck cancer.2019

    • Author(s)
      Matoba T, Imai M, Ohkura N, Kawakita D, Ijichi K, Toyama T, Morita A, Murakami S, Sakaguchi S, Yamazaki S.
    • Journal Title

      International Journal of Cancer

      Volume: 144(11) Issue: 11 Pages: 2811-2822

    • DOI

      10.1002/ijc.32024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 皮膚の樹状細胞と制御性T細胞のクロストークによる免疫制御2019

    • Author(s)
      山崎小百合, 森田明理
    • Journal Title

      医学のあゆみ

      Volume: 268 Pages: 1165-1169

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells2018

    • Author(s)
      Loh Jia Tong、Lim Thomas Jun Feng、Ikumi Kyoko、Matoba Takuma、Janela Baptiste、Gunawan Merry、Toyama Tatsuya、Bunjamin Maegan、Ng Lai Guan、Poidinger Michael、Morita Akimichi、Ginhoux Florent、Yamazaki Sayuri、Lam Kong-Peng、Su I-hsin
    • Journal Title

      iScience

      Volume: 10 Pages: 23-39

    • DOI

      10.1016/j.isci.2018.11.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TLRアゴニストを用いた抗癌免疫アジュバント療法2018

    • Author(s)
      志馬寛明, 松本美佐子, 山崎小百合, 瀬谷司
    • Journal Title

      Thrombosis Medicine

      Volume: 8 Pages: 97-104

    • Related Report
      2018 Annual Research Report
  • [Journal Article] TLRアゴニストを用いた抗癌免疫アジュバント療法2018

    • Author(s)
      志馬寛明、松本美佐子、山崎小百合、瀬谷司
    • Journal Title

      Thrombosis Medicine

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Ultraviolet B?Induced Maturation of CD11b-Type Langerin?Dendritic Cells Controls the Expansion of Foxp3+Regulatory T Cells in the Skin2017

    • Author(s)
      Yamazaki Sayuri、Odanaka Mizuyu、Nishioka Akiko、Kasuya Saori、Shime Hiroaki、Hemmi Hiroaki、Imai Masaki、Riethmacher Dieter、Kaisho Tsuneyasu、Ohkura Naganari、Sakaguchi Shimon、Morita Akimichi
    • Journal Title

      The Journal of Immunology

      Volume: 200 Issue: 1 Pages: 119-129

    • DOI

      10.4049/jimmunol.1701056

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis2017

    • Author(s)
      Ryoji Kubo, Shinnosuke Muramatsu, Yoko Sagawa, Chiyo Saito, Saori Kasuya, Akiko Nishioka, Emi Nishida, Sayuri Yamazaki, Akimichi Morita
    • Journal Title

      Journal of Dermatological Science

      Volume: 86 Issue: 1 Pages: 46-53

    • DOI

      10.1016/j.jdermsci.2017.01.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Skin dendritic cells expressing a unique set of genes associated with immunological tolerance are specialized to expand thymus-derived Foxp3+ regulatory T cells upon ultraviolet B exposure2019

    • Author(s)
      Yamazaki S, Odanaka M, Shime H, Imai M, Hemmi H, Kaisho T, Ohkura N, Sakaguchi S, Morita A.
    • Organizer
      Japan-Singapore International Skin Conference 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 頭頸部癌における制御性T細胞の新たな特徴2019

    • Author(s)
      的場拓磨、今井優樹、大倉永也、川北大介、伊地知圭、遠山竜也、森田明理、村上信五、坂口志文、山崎小百合
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Foxp3+ regulatory T cells are expanded by ultraviolet B-exposed PD-L1+ skin dendritic cell expressing a unique set of genes in a CSF1-independent manner.2018

    • Author(s)
      Yamazaki S, Odanaka M, Nishioka A, Kasuya S, Shime H, Hemmi H, Imai M, Riethmacher D, Kaisho T, Ohkura N, Sakaguchi S, Morita A.
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 紫外線で誘導される樹状細胞と制御性T細胞のクロストークによる免疫制御2018

    • Author(s)
      山崎小百合
    • Organizer
      第69回日本皮膚科学会中部支部学術大会特別講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 樹状細胞と制御性T細胞―二つのコントローラーによる免疫制御2018

    • Author(s)
      山崎小百合
    • Organizer
      第28回日本樹状細胞研究会 シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Dendritic cells expressing a unique set of genes associated with immunological tolerance are specialized to expand thymus-derived Foxp3+ regulatory T cells in the ultraviolet B-exposed skin2018

    • Author(s)
      Sayuri Yamazaki, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Akiko Nishioka, Hiroaki Hemmi, Tsuneyasu Kaisho, Naganari Ohkura, Shimon Sakaguchi, Akimichi Morita
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Hyperglycemia is associated with psoriatic inflammation in both humans and mice2018

    • Author(s)
      Mizuyu Odanaka, Kyoko Ikumi, Hiroaki Shime, Masaki Imai, Osamu Taguchi, Hiroaki Hemmi, Tsuneyasu Kaisho, Akimichi Morita, Sayuri Yamazaki
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A New Feature of Regulatory T Cells in Human Head and Neck Cancer2018

    • Author(s)
      Takuma Matoba, Masaki Imai, Naganari Ohkura, Daisuke Kawakita, Kei Ijichi, Tatsuya Toyama, Akimichi Morita, Shingo Murakami, Shimon Sakaguchi, Sayuri Yamazaki
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Successful treatment of psoriatic inflammation restores hyperglycemia2018

    • Author(s)
      Kyoko Ikumi, Mizuyu Odanaka, Hiroaki Shime, Masaki Imai, Osamu Taguchi, Hiroaki Hemmi, Tsuneyasu Kaisho, Sayuri Yamazaki, Akimichi Morita
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The critical role of dendritic cell subset in expanding Foxp3+ regulatory T cells in the murine skin after ultraviolet B exposure.2017

    • Author(s)
      Yamazaki, S., Nishioka, A., Kasuya, S., Odanaka, M., Hemmi, H., Imai, M., Riethmacher, D., Kaisho, T., Ohkura, N., Sakaguchi, S., Morita, A.
    • Organizer
      LC2017 15th International Workshop on Langerhans Cells. NewYork, USA
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 名古屋市立大学大学院医学研究科免疫学教室

    • URL

      https://www.nagoya-cu.ac.jp/med/labo/immune/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 名古屋市立大学大学院医学研究科免疫学分野

    • URL

      http://www.med.nagoya-cu.ac.jp/immunol.dir/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2019-12-27  

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