Understanding of detailed pathology and development of novel molecular targeted therapy for the treatment of refractory chronic inflammatory diseases based on the inflammatory cytokine IL-26
Project/Area Number |
20H03471
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49030:Experimental pathology-related
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Research Institution | Juntendo University |
Principal Investigator |
Morimoto Chikao 順天堂大学, 大学院医学研究科, 特任教授 (30119028)
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Co-Investigator(Kenkyū-buntansha) |
波多野 良 順天堂大学, 大学院医学研究科, 特任准教授 (30638789)
大沼 圭 順天堂大学, 大学院医学研究科, 非常勤講師 (10396872)
岩田 哲史 順天堂大学, 大学院医学研究科, 非常勤講師 (00396871)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | IL-26 / 炎症性サイトカイン / 慢性炎症 / 自己免疫疾患 / ヒト免疫 / IL-26中和抗体 / 関節炎モデル / 関節炎 / 炎症性腸疾患 / 移植片対宿主病 |
Outline of Research at the Start |
IL-26は多様な慢性炎症疾患で発現増加が報告されている新規炎症性サイトカインだが、マウスに欠損した遺伝子のため従来のマウス疾患モデルでは見逃されていたヒト炎症の重要な因子である。IL-26が多臓器線維化・過剰な血管新生を引き起こし、肺・肝臓など全身臓器の炎症や関節炎の増悪にも関与することを見出した。本研究では申請者ら独自のIL-26研究ツールを用いた疾患モデルにより、慢性炎症におけるIL-26の機能を解明し、新規抗炎症療法を開発するための基盤研究を行う。
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Outline of Final Research Achievements |
IL-26 is a Th17 cytokine, with its gene being absent in rodents. Without accessible animal models due partly to the absence of the IL-26 gene in mice, IL-26 role in inflammatory disorders is not clearly characterized. Utilizing human IL-26 bacterial artificial chromosome transgenic (hIL-26Tg) mice, we have investigated the in vivo effects of IL-26 in various inflammation models such as psoriasis model, colitis model, arthritis model and chronic graft-versus-host disease models. IL-26 is associated with the exacerbated inflammation and fibroproliferation. Moreover, IL-26 markedly enhanced the infiltration of T cells and neutrophils and augmented Th17 response associated with enhanced levels of G-CSF, IL-1β and IL-6. Taken together, our data elucidate the novel in vivo effects of IL-26 and strongly suggest that a humanized neutralizing anti-IL-26 monoclonal antibody may be a potential therapeutic agent for the treatment of refractory chronic inflammatory diseases.
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Academic Significance and Societal Importance of the Research Achievements |
近年、サイトカインやその受容体に結合してその機能を阻害する抗体医薬が様々な自己免疫疾患やアレルギー疾患の治療薬として承認されている。IL-26は主にTh17細胞が産生する炎症性サイトカインだが、マウスには欠損した遺伝子であり、従来のマウス疾患モデルでは見逃されていた因子であるため、まだその機能については明らかにすべき点は多い。 代表者らはヒトIL-26トランスジェニックマウスを用いて、様々な炎症性疾患モデルにおけるIL-26の役割を解明し、IL-26の中和抗体を開発した。IL-26抗体が炎症と組織の線維化を制御できる新たな治療薬となることが期待される。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Humanized anti-IL-26 monoclonal antibody as a novel targeted therapy for chronic graft-versus-host disease.2022
Author(s)
Hatano R, Itoh T, Otsuka H, Saeki H, Yamamoto A, Song D, Shirakawa Y, Iyama S, Sato T, Iwao N, Harada N, Aune TM, Dang NH, Kaneko Y, Yamada T, Morimoto C, Ohnuma K.
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Journal Title
Am J Transplant.
Volume: 22
Pages: 2804-2820
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Anti-Human CD9 Fab Fragment Antibody Blocks the Extracellular Vesicle-Mediated Increase in Malignancy of Colon Cancer Cells.2022
Author(s)
Santos MF, Rappa G, Fontana S, Karbanova J, Aalam F, Tai D, Li Z, Pucci M, Alessandro R, Morimoto C, Corbeil D, Lorico A.
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Journal Title
Cells.
Volume: 11
Issue: 16
Pages: 2474-2474
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Serum soluble CD26/DPP4 titer variation is a potential prognostic biomarker in cancer therapy with a humanized anti-CD26 antibody.2021
Author(s)
Kaneko Y, Hatano R, Hirota N, Isambert N, Trillet-Lenoir V, You B, Alexandre J, Zalcman G, Valleix F, Podoll T, Umezawa Y, Takao S, Iwata S, Hosono O, Taguchi T, Yamada T, Dang NH, Ohnuma K, Angevin E, Morimoto C.
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Journal Title
Biomark Res
Volume: 9
Issue: 1
Pages: 21-21
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Single-cell atlas of colonic CD8+ T-cells in ulcerative colitis.2020
Author(s)
Corridoni D, Antanaviciute A, Gupta T, Fawkner-Corbett D, Aulicino A, Jagielowicz M, Parikh K, Repapi E, Taylor S, Ishikawa D, Hatano R, Yamada T, Xin W, Slawinki H, Bowden R, Napolitani G, Brain O, Morimoto C, Koohy H, Simmons A.
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Journal Title
Nat Med
Volume: 26
Issue: 9
Pages: 1480-1490
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] CD26/dipeptidyl-peptidase IVは機械的かゆみの調節因子である.2021
Author(s)
古宮栄利子, 冨永光俊, 波多野良, 外山扇雅, 伊藤匠, 鎌田弥生, 本田耕太郎, 大沼圭, 森本幾夫, 高森建二.
Organizer
第26回日本病態プロテアーゼ学会, 口頭発表, Web開催
Related Report
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[Presentation] Anti-interleukin-26 therapy for the control of chronic inflammation in GVHD.2021
Author(s)
Hatano R, Otsuka H, Itoh T, Saeki H, Yamamoto A, Shirakawa Y, Iyama S, Iwao N, Sato T, Yamada T, Morimoto C, Ohnuma K.
Organizer
第83回日本血液学会, 口頭発表, Web開催
Related Report
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[Presentation] CD26/DPPIV regulates mechanical alloknesis at the periphery.2021
Author(s)
Komiya E, Tominaga M, Hatano R, Itoh T, Honda K, Toyama S, Kamata Y, Otsuka H, Ohnuma K, Morimoto C, Takamori K.
Organizer
11th World Congress on Itch (WCI), 口頭発表, Web開催
Related Report
Int'l Joint Research
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[Presentation] Mu-opioid ligand endomorphin induces alloknesis at the periphery.2021
Author(s)
Komiya E, Tominaga M, Hatano R, Itoh T, Honda K, Toyama S, Kamata Y, Otsuka H, Ohnuma K, Morimoto C, Takamori K.
Organizer
第46回日本研究皮膚科学会, 口頭発表, Web開催
Related Report
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[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
The 45th Annual Meeting of the Japanese Society for Investigative Dermatology
Related Report
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