2020 Fiscal Year Final Research Report

Scientific research on development of anti-fibrotic agent targeting multi-organ profibrotic factor IL-26 in GVHD

Research Project

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Project/Area Number	18H02782
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 52050:Embryonic medicine and pediatrics-related
Research Institution	Juntendo University
Principal Investigator	Kei Ohnuma 順天堂大学, 医学(系)研究科(研究院), 准教授 (10396872)
Co-Investigator(Kenkyū-buntansha)	森本幾夫順天堂大学, 医学(系)研究科(研究院), 特任教授 (30119028) 岩田哲史順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (00396871) 岩尾憲明順天堂大学, 医学部, 准教授 (00309139)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	IL-26 / 慢性GVHD / 線維化 / 造血幹細胞移植
Outline of Final Research Achievements	There are increasing more and more numbers of patients with chronic inflammation-related organ fibrosis disorders including diabetic nephropathy, arteriolosclerosis, age-related nephrosclerosis, and chronic obstructive pulmonary diseases. Control of systemic fibrosis is also indispensable in realization of regenerative medicine. Moreover, treatment of organ fibrosis is an important target for extension of healthy life expectancy of the people by preventing deterioration of lifestyle-related diseases and rare intractable immune disorders. In this study, we identified the key mechanisms of organ fibrosis by means of IL-26, a unique cytokine in human, which have been overlooked in murine models. We obtained the promising results in developing a novel antifibrotic agent against intractable organ fibrosis. Our results on a new antifibrotic treatment also possibley provide a proper condition for organ regeneration such as iPS cell-based regenerative therapy.
Free Research Field	小児科
Academic Significance and Societal Importance of the Research Achievements	臓器の線維化は、慢性炎症や加齢による組織の老化と密接な関連があり、臓器線維症は今後益々増加する疾患である。現在、特発性肺線維症に対する抗線維化薬としてピルフェニドンとニンテダニブが薬事承認を受けている。しかし、消化管・皮膚障害、血栓症等の重篤な副作用が出現する。一方、本研究の標的分子IL-26は、線維化カスケードループの最上流に位置するエフェクタ分子という点で画期的な抗線維化薬の創薬シーズであり、われわれは、治療困難であった臓器線維症の独創的な創薬に繋がる成果を得た。国民の健康寿命の延伸と健康格差の縮小に貢献し、またiPS細胞等の再生医療に対しても適切な臓器再生の場を提供することができる。