Development of a novel therapy for refractory inflammatory diseases targeting an inflammatory cytokine IL-26

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: Hatano Ryo 順天堂大学, 医学(系)研究科(研究院), 特任助教 (30638789)
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

免疫学

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。