| Project/Area Number |
17K10008
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Juntendo University |
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Principal Investigator |
Hatano Ryo 順天堂大学, 医学(系)研究科(研究院), 特任助教 (30638789)
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| Co-Investigator(Kenkyū-buntansha) |
岩田 哲史 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (00396871)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | IL-26 / 中和抗体 / 乾癬 / 血管新生 / 慢性炎症疾患 / 分子標的療法 / 炎症性サイトカイン / 炎症性腸疾患 / 自己免疫疾患 / 慢性GVHD / CD26共刺激 / 慢性炎症 / Th17 / CD26 |
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| Outline of Final Research Achievements |
Due to the deficiency of the gene encoding IL-26 in mice, the precise functions and identification of target cells of IL-26 in inflammatory disorders remain to be elucidated. From these reasons, our group has developed human IL-26 transgenic (hIL-26Tg) mice. In the present study, we found that vascularization and immune cell infiltration were dramatically enhanced in hIL-26Tg mice in the imiquimod-induced psoriasis-like murine model. Moreover, we have shown that IL-26 directly acts on vascular endothelial cells to promote proliferation and tube formation at a similar level as VEGF.In addition, we have succeeded in developing novel neutralizing anti-human IL-26 monoclonal antibodies (mAbs) which can inhibit the biological functions of IL-26.
Our newly developed anti-human IL-26 mAb is a potential therapeutic agent for the treatment of diverse chronic inflammatory diseases including psoriasis, inflammatory bowel diseases, chronic graft-versus-host disease, lung fibrosis and so on.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らはCD26分子を介したヒトT細胞の活性化が、炎症性サイトカインIL-26の産生に極めて重要であることを明らかにした。IL-26は多様な機能が報告されているが、マウスやラットに欠損した遺伝子であることもあり、炎症病態における役割について解明されていない点が多い。申請者グループは、炎症環境下でヒトIL-26の発現が誘導されるヒトIL-26トランスジェニックマウスを開発し、炎症病態におけるIL-26の新たな機能の解明に取り組むとともに、IL-26の中和モノクローナル抗体の樹立にも成功した。これらのツールを用いて、難治性の慢性炎症疾患に対する革新的なIL-26分子標的療法の確立を進めていく。
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