Development of new refractory asthma treatments of targeting OX40 ligand.

抗类固醇T细胞被认为是难治性哮喘的原因之一。为了激活T细胞，两个受体必须发出信号。一种是通过T细胞受体（TCR）传递抗原特异性信号，另一种是通过共刺激分子传递抗原非特异性信号。已知，与仅刺激TCR信号相比，同时刺激TCR信号和共刺激信号时，T细胞的类固醇抗性增加更多。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细胞的类固醇敏感性。观察到低浓度类固醇可降低OX40缺陷小鼠的哮喘反应（嗜酸性粒细胞浸润和气道高反应性），而野生型小鼠则无此作用。因此，认为OX40配体可能成为开发难治性哮喘药物的新分子靶点。

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.