Establishment of an IL-1-related gene-manipulated mice library, aiming at uncovering pathophysiology of disease from a view point of systems biology

建立IL-1相关基因操作小鼠文库，旨在从系统生物学角度揭示疾病的病理生理学

• 批准号: 20220009
• 负责人: IWAKURA Yoichiro
• 金额: $ 64.98万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20220009/
• 关键词: サイトカイン; 疾患モデル動物; 自己免疫疾患; Th17細胞; 関節リウマチ; 間接リウマチ

The project’s aim is to deeply understand the pathological and physiological roles of IL-1 and IL-1-relating genes in maintaining homeostasis and developing diseases in the immune, the nervous, and the endocrine system. In addition to evaluating the pathophysiological role of these genes, we intended to establish a system of bio-source to provide the gene-manipulated mice with all researchers. We newly generated five gene-targeting mice, which have been finished in backcrossing toward C57BL6/c background, and four additional gene-targeting mice (DCIR, IL-1R2, IL-1F6, and SCPL) were backcrossed to C57BL6/c background. We demonstrated that IL-1-related genes were involved in the regulation of bone metabolism and the development of autoimmune diseases, like arthritis. Moreover, IL-1 was a mediator in controlling activity of the nervous system and had a direct effect on lipid metabolism. On the basis of our analysis in gene-targeting mice, these mice are novel useful disease-models for analyzing the pathology of bony and autoimmune diseases. Finally, we set up the system that supplies gene-manipulated mice that we generated to all researchers, contributing to the progress of research horizons in laboratory animal.

该项目的目的是深入了解IL-1及其相关基因在维持免疫、神经和内分泌系统内稳态和发生疾病中的病理生理作用。除了评估这些基因的病理生理作用外，我们还打算建立一个生物来源系统，为基因操作小鼠提供所有的研究人员。我们新生成了5只基因靶向小鼠，并完成了C57BL6/c背景的回交，另外4只基因靶向小鼠（DCIR、IL-1R2、IL-1F6和SCPL）也完成了C57BL6/c背景的回交。我们证明了il -1相关基因参与骨代谢的调节和自身免疫性疾病的发展，如关节炎。此外，IL-1是控制神经系统活性的介质，对脂质代谢有直接影响。根据我们对基因靶向小鼠的分析，这些小鼠是分析骨骼和自身免疫性疾病病理的新的有用疾病模型。最后，我们建立了一个系统，将我们生产的基因操纵小鼠提供给所有的研究人员，促进了实验动物研究视野的进步。

项目成果

Apoptotic cells activate NKT cells through T cell Ig-like mucin-like-1 resulting in airway hyperreactivity.

• DOI: 10.4049/jimmunol.1001116
• 发表时间: 2010-11-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Lee HH;Meyer EH;Goya S;Pichavant M;Kim HY;Bu X;Umetsu SE;Jones JC;Savage PB;Iwakura Y;Casasnovas JM;Kaplan G;Freeman GJ;DeKruyff RH;Umetsu DT
• 通讯作者: Umetsu DT

Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease

• DOI: 10.1182/blood-2009-05-219402
• 发表时间: 2009-10-01
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Yi, Tangsheng;Chen, Ying;Zeng, Defu
• 通讯作者: Zeng, Defu

IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells.

• DOI: 10.1084/jem.20071133
• 发表时间: 2008-05-12
• 期刊: The Journal of experimental medicine
• 作者: Tajima M;Wakita D;Noguchi D;Chamoto K;Yue Z;Fugo K;Ishigame H;Iwakura Y;Kitamura H;Nishimura T
• 通讯作者: Nishimura T

Control of TH17 cells occurs in the small intestine.

• DOI: 10.1038/nature10228
• 发表时间: 2011-07-17
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Esplugues, Enric;Huber, Samuel;Gagliani, Nicola;Hauser, Anja E.;Town, Terrence;Wan, Yisong Y.;O'Connor, William, Jr.;Rongvaux, Anthony;Van Rooijen, Nico;Haberman, Ann M.;Iwakura, Yoichiro;Kuchroo, Vijay K.;Kolls, Jay K.;Bluestone, Jeffrey A.;Herold, Kevan C.;Flavell, Richard A.
• 通讯作者: Flavell, Richard A.

Protective role of IL-1β against post-arthroplasty Staphylococcus aureus infection.

• DOI: 10.1002/jor.21414
• 发表时间: 2011-10
• 期刊: JOURNAL OF ORTHOPAEDIC RESEARCH
• 影响因子: 2.8
• 作者: Bernthal, Nicholas M.;Pribaz, Jonathan R.;Stavrakis, Alexandra I.;Billi, Fabrizio;Cho, John S.;Ramos, Romela Irene;Francis, Kevin P.;Iwakura, Yoichiro;Miller, Lloyd S.
• 通讯作者: Miller, Lloyd S.