Development of the antibody medical treatment to autoimmune and asthmatic diseases based on new target molecule.

基于新靶点分子的抗体药物治疗自身免疫性疾病和哮喘疾病的开发。

• 批准号: 23390260
• 负责人: OKUMURA Ko
• 金额: $ 12.31万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390260/
• 关键词: 自己免疫疾患; 関節リウマチ; 抗体療法; 喘息; アレルギー･喘息; アレルギー・喘息; TIM-4; コラーゲン誘発性関節炎; 抗炎症作用

In this study, we demonstrated a critical contribution of TIM-4 to the development of collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA), which are well-established animal model for the human rheumatoid arthritis. Administration of anti-TIM-4 mAb significantly inhibited the development of CIA and CAIA with a concomitant decrease of IL-6 and IL-1 beta in the ankle joints. Importantly, high levels of soluble TIM-4 were detected in sera of CIA mice as compared with naive mice. Moreover, soluble TIM-4 stimulation significantly induced IL-6 and TNF-alpha production by macrophages. These effects might be mediated by TIM-4-LMIR5 interaction. It is noteworthy that the inhibitory effects against the development and progression of arthritis by anti-TIM-4 mAb were observed when anti-TIM-4 mAb was administrated after the onset or even after the establishment of arthritis. TIM-4 thus represents a novel target for intervention of rheumatoid arthritis.

在这项研究中，我们证明了TIM-4对胶原诱导的关节炎（CIA）和胶原抗体诱导的关节炎（CAIA）的发展的关键贡献，这是人类类风湿性关节炎的成熟动物模型。抗TIM-4 mAb的给药显著抑制了CIA和CAIA的发展，同时踝关节中的IL-6和IL-1 β降低。重要的是，与幼稚小鼠相比，在CIA小鼠的血清中检测到高水平的可溶性TIM-4。此外，可溶性TIM-4刺激显著诱导巨噬细胞产生IL-6和TNF-α。这些作用可能是由TIM-4-LMIR 5相互作用介导的。值得注意的是，当在关节炎发作后或甚至在关节炎建立后施用抗TIM-4 mAb时，观察到抗TIM-4 mAb对关节炎的发展和进展的抑制作用。因此，TIM-4代表了类风湿性关节炎干预的新靶点。

项目成果

Serial transfere of anergy status induced by TSST-1 into newly stimulated T cells

将 TSST-1 诱导的无反应状态连续转移到新刺激的 T 细胞中

• 发表时间: 2013
• 作者: N. Negishi;T. Sato;Y. Kametani;S. Hori;K. Okumura;S. Habu
• 通讯作者: S. Habu

マスト細胞におけるGATA3の機能解析

肥大细胞中GATA3的功能分析

• 发表时间: 2012
• 作者: Toki T;Adachi S;et al;坂部正英 森岡崇 井口朋子 井岡朋子 水田賢 八反丸美和 佐藤玄基 伊藤宗洋 林寿来 Manuel Utset Eric Olson 木村弘 中川修;八代拓也
• 通讯作者: 八代拓也

ヒトマスト細胞、好塩基球におけるST2遺伝子の発現調節

人类肥大细胞和嗜碱性粒细胞中 ST2 基因表达的调节

• 发表时间: 2012
• 作者: Seki M;Yoshida K;Shiraishi Y;Shimamura T;Sato Y;Nishimura R;Okuno Y;Chiba K;Tanaka H;Kato K;Kato M;Hanada R;Nomura Y;Park MJ;Ishida T;Oka A;Igarashi T;Miyano S;Hayashi Y;Ogawa S;Takita J;前田啓子
• 通讯作者: 前田啓子

Possible roles of host defense protein S100A7/psoriasin in skin barrier functions

宿主防御蛋白 S100A7/牛皮癣素在皮肤屏障功能中的可能作用

• 发表时间: 2012
• 作者: 2. Mori M;Hiwatari M;Takita J;Ida K;Kawaguchi H;Fumihiro Hattori
• 通讯作者: Fumihiro Hattori

樹状細胞のMHC classII,CD11c発現における転写調節因子PU.1の役割

转录调节因子 PU.1 在 MHC II 类、树突状细胞 CD11c 表达中的作用

• 发表时间: 2011
• 作者: Hasegawa D;Adachi S;et al.;北村奈緒
• 通讯作者: 北村奈緒