Development of new refractory asthma treatments of targeting OX40 ligand.

开发针对 OX40 配体的新型难治性哮喘治疗方法。

• 批准号: 24790093
• 负责人: OHTOMO TAKAYUKI
• 金额: $ 2.83万
• 依托单位: Tokyo University of Pharmacy and Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790093/
• 关键词: 気管支喘息; アレルギー; T細胞

Steroid-resistant T cell is thought to be one of the causes to refractory asthma. It is necessary for two receptors signaling in order to activate T cells. One is antigen-specific signal through the T cell receptor (TCR), and the other is antigen non-specific signal through the co-stimulatory molecules. It is known that the steroid resistance of T cell more increases when stimulated both TCR signal and co-stimulatory signals compared to only TCR signal. OX40 ligand is one of the co-stimulatory molecules. In this study, we investigated steroids-sensitivity of T cell under the condition of OX40 ligand defect. It was observed that asthmatic reaction (eosinophil infiltration and airway hyperresponsiveness) of OX40 deficient mice was reduced by low-concentrated steroids, but that of wild type mice was not. Thus, it is thought that OX40 ligand could be a new molecule target of development of refractory asthma drug.

类固醇抗性T细胞被认为是难治性哮喘的原因之一。激活T细胞需要两种受体的信号传导。一种是通过T细胞受体(TCR)传递的抗原特异性信号，另一种是通过共刺激分子传递的抗原非特异性信号。已知，当TCR信号和共刺激信号同时刺激时，T细胞的类固醇抵抗比单独刺激TCR信号时增加得更多。OX40配体是共刺激分子之一。在本研究中，我们研究了OX40配体缺陷条件下T细胞对类固醇的敏感性。低浓度类固醇对OX40基因缺陷小鼠的哮喘反应(嗜酸性粒细胞浸润和气道高反应性)有抑制作用，而对野生型小鼠则无明显影响。因此，OX40配体可能成为开发难治性哮喘药物的一个新的分子靶点。

项目成果

非アトピー型喘息のマウスモデル作成と解析

非特应性哮喘小鼠模型的创建和分析

• 发表时间: 2013
• 作者: 神山智;大友暁美;大友隆之;山口美也子;飯島葉;森晶夫
• 通讯作者: 森晶夫

Adoptive transfer of Th clones confer late-phase asthmatic response in mice.

Th 克隆的过继转移赋予小鼠晚期哮喘反应。

• 发表时间: 2013
• 作者: Mori;A.;Kouyama;S.;Yamaguchi;M.;Iijima;Y.;Itoh;J.;Saito;N.;Minami;T .;Watarai;K.;Mitsui;C.;Oshikata;C.;Tanimoto;H.;Fukutomi;Y.;Sekiya;K. ;Tsuburai;T.;Taniguchi;M.;Maeda;Y.;Ohtomo;M.;Hasegawa;M.;Akiyama;K.;Ohtomo;T.
• 通讯作者: T.

Adoptive transfer of Th clones confer late-phase asthmatic response in mice, European Academy of Allergy and Clinical Immunology-World Allergy

欧洲过敏和临床免疫学学会称，Th 克隆的过继转移赋予小鼠晚期哮喘反应 - 世界过敏

• 发表时间: 2013
• 作者: Mori;A.;Kouyama;S.;Yamaguchi;M.;Iijima;Y.;Itoh;J.;Saito;N.;Minami;T.;Watarai;K.;Mitsui;C.;Oshikata;C.;Tanimoto;H.;Fukutomi;Y.;Sekiya;K.;Tsuburai;T.;Taniguchi;M.;Maeda;Y.;Ohtomo;M.;Hasegawa;M.;Akiyama;K.;Ohtomo;T.;Ka
• 通讯作者: Ka