Development of new refractory asthma treatments of targeting OX40 ligand.

• Project/Area Number: 24790093
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: OHTOMO TAKAYUKI 東京薬科大学, 薬学部, 助教 (90463108)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 気管支喘息 / アレルギー / T細胞

Research Abstract

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.

Research Products

• [Presentation] 非アトピー型喘息のマウスモデル作成と解析 (2013)
  • Author(s): 神山智、大友暁美、大友隆之、山口美也子,飯島葉、森晶夫
  • Organizer: 第44回日本職業・環境アレルギー学会総会・学術大会
  • Place of Presentation: 相模原市
• [Presentation] Adoptive transfer of Th clones confer late-phase asthmatic response in mice, European Academy of Allergy and Clinical Immunology-World Allergy (2013)
  • Author(s): 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., Kaminuma, O
  • Organizer: Organization World Allergy &Asthma Congress
  • Place of Presentation: Italy
• [Presentation] Adoptive transfer of Th clones confer late-phase asthmatic response in mice. (2013)
  • Author(s): 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., and Kaminuma, O.
  • Organizer: European Academy of Allergy and Clinical Immunology-World Allergy Organization World Allergy & Asthma Congress 2013
  • Place of Presentation: Milan, Italy