Development of new refractory asthma treatments of targeting OX40 ligand.

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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.