Development of human allergic asthma models using next-generation humanized mice for drug discovery

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07103
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Central Institute for Experimental Animals
• Principal Investigator: Ito Ryoji 公益財団法人実験動物中央研究所, 実験動物研究部, 室長代理 (60425436)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ヒト化マウス / 気管支喘息 / アレルギー

Outline of Final Research Achievements

We aim to establish a preclinical animal model of asthmatic airway inflammation using humanized IL-3/GM-CSF or IL-3/GM-CSF/IL-5 transgenic (Tg) NOG mice and investigate the roles of human type-2 immune responses in the asthmatic mice. Several important characteristics of asthma―such as AHR, goblet cell hyperplasia, T cell infiltration, IL-13 production, and periostin secretion―were induced in IL-3/GM-CSF Tg mice by intratracheally administered human IL-33. In addition to these characteristics, human eosinophilic inflammation was observed in IL-3/GM-CSF/IL-5 Tg mice. Furthermore, treatment of the humanized mice with an anti-human IL-13 antibody significantly suppressed these characteristics. Therefore, the humanized mice may enhance our understanding of the pathophysiology of allergic disorders and facilitate the preclinical development of new therapeutics for IL-33-mediated type-2 inflammation in asthma.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究によりヒトアレルギー性喘息モデルが確立されれば、これまで不可能であったヒト喘息病態の生体内モニタリングが可能となり、様々なヒト免疫細胞が関与する喘息発症までの一連の生体内経路を解析できる。また、抗アレルギー薬の薬効評価や安全性試験を生体内で行う事が可能となるため、基礎、臨床の両分野において幅広く利用される実験動物となり得る。将来的には食物アレルギー、アトピー性皮膚炎など、様々なヒトアレルギー疾患を発症するモデルマウスとして世界中の研究者への頒布体制を整え、全世界のアレルギー研究に貢献したいと考えている。