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Establishment of the molecular basis of new therapies for intractable itch and pathology in psoriasis

Research Project

Project/Area Number 17K16353
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionJuntendo University

Principal Investigator

Komiya Eriko  順天堂大学, 医学(系)研究科(研究院), 特任助教 (90647009)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords乾癬 / かゆみ / 神経ペプチド / CD26 / DPPIV / IL-26 / CD26-DPPIV
Outline of Final Research Achievements

CD26 is a multifunctional protein with dipeptidyl peptidase IV (DPPIV) enzyme activity and is highly expressed in the sera of psoriasis patients. When we established psoriasis models, CD26 transgenic mice displayed exacerbation of the number of scratching behavior, and psoriatic pathology, compared with wildtype. Therefore, we aimed to develop a new treatment for psoriasis that acts on both itch and pathology by targeting the CD26 molecule.
The results obtained showed that CD26 exacerbated itch by its DPPIV enzyme activity, thorough the degradation of substance-P (SP), which is a member of neuropeptides. In contrast to the preliminary experiment,CD26 itself did not exacerbate the pathology, we identified interleukin 26 (IL-26), which is induced by CD26, exacerbated psoriatic pathology by its angiogenesis activity.

Academic Significance and Societal Importance of the Research Achievements

かゆみは、乾癬の患者さんの約6-9割が経験し、乾癬の症状の中でももっともつらいものうちの1つである。また、乾癬のかゆみには既存の抗ヒスタミン薬に対し、効果を示さないものが多く存在しており、その治療法の開発は急務であると言える。今回の結果は、乾癬のかゆみの増悪メカニズムの一端を明らかにしたのと同時に、CD26が発現促進しているIL-26の乾癬における紅斑(血管新生)促進メカニズムについても明らかにし、抗IL-26抗体が乾癬症状を抑えることも実験モデルで示した。
これらの結果を組み合わせることで、乾癬の病状とかゆみに対して効果的な新規治療法を確立できる可能性が示された。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2021 2020 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Molecular and Cellular Mechanisms of Itch in Psoriasis.2020

    • Author(s)
      Komiya E, Tominaga M, Kamata Y, Suga Y, Takamori K.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 21 Pages: 8406-8406

    • DOI

      10.3390/ijms21218406

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Calcium-inducible MAPK/AP-1 signaling drives semaphorin 3A expression in normal human epidermal keratinocytes.2020

    • Author(s)
      Kamata Y, Tominaga M, Umehara Y, Honda K, Kamo A, Moniaga CS, Komiya E, Toyama S, Suga Y, Ogawa H, Takamori K
    • Journal Title

      J Invest Dermatol.

      Volume: ー Issue: 7 Pages: 1346-1354

    • DOI

      10.1016/j.jid.2020.01.001

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of novel anti-IL-26 neutralizing monoclonal antibodies for the treatment of inflammatory diseases including psoriasis.2019

    • Author(s)
      Hatano R, Itoh T, Otsuka H, Okamoto S, Komiya E, Iwata S, Aune TM, Dang NH, Kuwahara-Arai K, Ohnuma K, Morimoto C.
    • Journal Title

      mabs.

      Volume: 11 Issue: 8 Pages: 1428-1442

    • DOI

      10.1080/19420862.2019.1654305

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of novel monoclonal antibodies with specific binding affinity for denatured human CD26 in formalin-fixed paraffin-embedded and decalcified specimens2019

    • Author(s)
      Hatano R, Yamada T, Madokoro H, Otsuka H, Komiya E, Itoh T, Narita Y, Iwata S, Yamazaki H, Matsuoka S, Dang NH, Morimoto C
    • Journal Title

      PLoS ONE

      Volume: 14 Issue: 6 Pages: e0218330-e0218330

    • DOI

      10.1371/journal.pone.0218330

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological effects of IL-26 on T cell-mediated skin inflammation, including psoriasis.2019

    • Author(s)
      Itoh T, Hatano R, Komiya E, Otsuka H, Narita Y, Aune TM, Dang NH, Matsuoka S, Naito H, Tominaga M, Takamori K, Morimoto C, Ohnuma K.
    • Journal Title

      J Invest Dermatol

      Volume: 139 Issue: 4 Pages: 878-889

    • DOI

      10.1016/j.jid.2018.09.037

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel role for CD26/dipeptidyl peptidase IV as a therapeutic target in selected immune disorders and cancers.2018

    • Author(s)
      Kei Ohnuma, Ryo Hatano, Eriko Komiya, Haruna Otsuka, Takumi Itoh, Noriaki Iwao, Yutaro Kaneko, Taketo Yamada, Hon H. Dang, Chikao Morimoto
    • Journal Title

      Front Biosci

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A possible role for CD26/DPPIV enzyme activity in the regulation of psoriatic pruritus2017

    • Author(s)
      Komiya, E. Hatano, R. Otsuka, H. Itoh, T. Yamazaki, H. Yamada, T. Dang, N. H. Tominaga, M. Suga, Y. Kimura, U. Takamori, K. Morimoto, C. Ohnuma, K.
    • Journal Title

      J Dermatol Sci

      Volume: 印刷中 Issue: 3 Pages: 212-221

    • DOI

      10.1016/j.jdermsci.2017.03.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 末梢mu-オピオイドによるアロネーシス制御機構の解明2021

    • Author(s)
      古宮栄利子, 冨永光俊, 大沼圭, 森本幾夫, 髙森建二
    • Organizer
      第29回国際かゆみシンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] Endomorphin preferentially induces mechanical alloknesis under the control of DPPIV enzyme2020

    • Author(s)
      Eriko Komiya, Ryo Hatano, Takumi Itoh, Kotaro Honda, Yayoi Kamata, Sumika Toyama, Catharina Sagita Moniaga, Haruna Otsuka, Nobuaki Takahashi, Kei Ohnuma, Mitsutoshi Tominaga, Chikao Morimoto, Kenji Takamori
    • Organizer
      日本研究皮膚科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CD26/DPPIV regulates mechanical itch by enzymatic degradation of mu-opioid receptor ligands.2019

    • Author(s)
      Eriko Komiya, Ryo Hatano, Takumi Itoh, Haruna Otsuka, Kei Ohnuma, Mitsutoshi Tominaga , Chikao Morimoto, Kenji Takamori
    • Organizer
      24th World Congress of Dermatology (WCD)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Possible role for CD26/DPPIV in regulating mechanical itch (Alloknesis)2019

    • Author(s)
      Eriko Komiya, Ryo Hatano, Takumi Itoh, Haruna Otsuka,Yayoi Kamata, Kotaro Honda, Sumika Toyama, Catharina Sagita Moniaga, Kei Ohnuma, Mitsutoshi Tominaga, Chikao Morimoto, Kenji Takamori
    • Organizer
      28th European Academy of Dermatology and Venereology (EADV) Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Possible regulation of mechanical itch by CD26/DPPIV2019

    • Author(s)
      Eriko Komiya, Ryo Hatano, Takumi Itoh, Haruna Otsuka, Yayoi Kamata, Kotaro Honda, Sumika Toyama, Catharina Sagita Moniaga, Kei Ohnuma, Mitsutoshi Tominaga, Chikao Morimoto, Kenji Takamori
    • Organizer
      10th World Congress on Itch (WCI)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] CD26/ dipeptidyl-peptidase IVは機械的かゆみの抑制因子である2019

    • Author(s)
      古宮栄利子、波多野良、冨永光俊、伊藤匠、鎌田弥生、本田耕太郎、外山扇雅、カタリナサギタモニアガ、大沼圭、森本幾夫、高森建二
    • Organizer
      日本病態プロテアーゼ学会
    • Related Report
      2019 Research-status Report
  • [Presentation] オピオイドによるかゆみ過敏の誘発とその調節機構の解明2019

    • Author(s)
      古宮 栄利子
    • Organizer
      環境医学研究所 順天堂かゆみ研究センター 第5回学術シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] CD26分子はDPPIV酵素活性によって乾癬のかゆみを調節する2018

    • Author(s)
      古宮栄利子, 波多野良, 大塚春奈, 伊藤匠, 大沼圭, 冨永光俊, 森本幾夫, 高森建二
    • Organizer
      第33回日本乾癬学会
    • Related Report
      2018 Research-status Report
  • [Presentation] CD26/DPPIVはエンドモルフィンによる機械的かゆみを制御する2018

    • Author(s)
      古宮栄利子, 波多野良, 伊藤匠, 松田浩則, 大沼圭, 森本幾夫, 冨永光俊, 高森建二
    • Organizer
      第28回国際かゆみシンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 機械的かゆみの調節メカニズムの解明2018

    • Author(s)
      古宮栄利子, 波多野良, 大塚春奈, 伊藤匠, 松田浩則, 須賀康, 大沼圭, 冨永光俊, 森本幾夫, 髙森建二
    • Organizer
      第82回日本皮膚科学会東京支部
    • Related Report
      2018 Research-status Report
  • [Presentation] 加齢皮膚で誘発される機械的かゆみ調節機構の解明2018

    • Author(s)
      冨永光俊, 波多野良, 伊藤匠, 大塚春奈, 本田耕太郎, 外山扇雅, 鎌田弥生, 大沼圭, 森本幾夫, 高森建二
    • Organizer
      第15回加齢皮膚医学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 乾癬における新規炎症性サイトカインIL-26の役割と分子標的療法の開発2018

    • Author(s)
      伊藤匠, 波多野良, 古宮栄利子, 大塚春奈, 冨永光俊, 高森建二, 森本幾夫, 大沼圭
    • Organizer
      第33回日本乾癬学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Interleukin-26-targeted therapy for the control of chronic GVHD2018

    • Author(s)
      Ryo Hatano, Haruna Otsuka, Eriko Komiya, Takumi Itoh, Naoki Iwao, Taketo Yamada, Chikao Morimoto, Kei Ohnuma
    • Organizer
      第80 回日本血液学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 加齢皮膚におけるアロネーシスの発症メカニズムの解明と治療法の開発2018

    • Author(s)
      冨永光俊, 古宮栄利子, 本田耕太郎, 外山扇雅, 鎌田弥生,高森建二
    • Organizer
      第15回加齢皮膚医学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] The regulation of pruritus in psoriasis and atopic dermatitis-a possible role for CD26/DPPIV2017

    • Author(s)
      Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Hiroto Yamazaki, Yasushi Suga, Utako Kimura, Taketo Yamada, Mitsutoshi Tominaga, Kenji Takamori , Kei Ohnuma, Chikao Morimoto
    • Organizer
      9th World congress on itch
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] CD26/DPPIV regulates mechanical itch in a mechanistically distinct manner from chemical itch.2017

    • Author(s)
      Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Hiroto Yamazaki, Mitsutoshi Tominaga, Kenji Takamori, Kei Ohnuma, Chikao Morimoto
    • Organizer
      日本研究皮膚科学会 第42回年次学術大会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 急性GVHDマウスモデルにおけるHMGB1の動態に関する検討2017

    • Author(s)
      岩尾憲明、大沼圭、大塚春奈、波多野良、古宮栄利子、伊藤匠、森本幾夫
    • Organizer
      第40回日本造血細胞移植学会
    • Related Report
      2017 Research-status Report
  • [Book] Advances in Medicine and Biology  The use of the humanized anti-CD26 monoclonal antibody YS110 as a novel targeted therapy for refractory cancers and immune disorders2018

    • Author(s)
      Ryo Hatano, Kei Ohnuma K, Taketo Yamada, Toshihiro Okamoto, Eriko Komiya, Haruna Otsuka, Takumi Itoh, Hiroto Yamazaki, Noriaki Iwao, Yutaro Kaneko, Nam H. Dang, Chikao Morimoto
    • Total Pages
      44
    • Publisher
      Nova Science Publishers, Inc.
    • ISBN
      9781536133486
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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