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

• Project/Area Number: 17K16353
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Juntendo 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: ¥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。

Research Products

• [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
  • 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
  • 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
  • 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 specimens (2019)
  • 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
  • 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
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A possible role for CD26/DPPIV enzyme activity in the regulation of psoriatic pruritus (2017)
  • 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
  • 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
• [Presentation] Endomorphin preferentially induces mechanical alloknesis under the control of DPPIV enzyme (2020)
  • 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
• [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)
  • 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
  • Int'l Joint Research
• [Presentation] Possible regulation of mechanical itch by CD26/DPPIV (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: 10th World Congress on Itch (WCI)
  • 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
• [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
  • 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
• [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
  • 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
• [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
• [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
• [Presentation] Interleukin-26-targeted therapy for the control of chronic GVHD (2018)
  • 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
• [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
• [Presentation] The regulation of pruritus in psoriasis and atopic dermatitis-a possible role for CD26/DPPIV (2017)
  • 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
  • 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
• [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
• [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 disorders (2018)
  • 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