The pathogenic role of Arid5a in infection and autoimmunity.

• Project/Area Number: 26860328
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: MASUDA Kazuya 大阪大学, 免疫学フロンティア研究センター, 寄附研究部門助教 (70722544)
• Research Collaborator: KISHIMOTO Tadamitsu 大阪大学, 免疫学フロンティア研究センター, 特任教授 (10093402) ; TAKEUCHI Osamu 京都大学, ウイルス研究所, 教授 (10379092)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自己免疫疾患 / T細胞過剰活性化 / RNA安定性制御 / RNA結合タンパク質 / 転写後調節 / IL-6 mRNA / STAT分子 / Th17細胞 / Arid5a / Regnase-1 / インフルエンザ / 感染・炎症 / サイトカインストーム

Outline of Final Research Achievements

It has been reported that high expression of IL-6 is associated with the patients with rheumatoid arthritis. Recently, we found that AT-rich interactive domain containing 5a (Arid5a) stabilize IL-6 mRNA through binding to IL-6 3'UTR, which in turn elevates IL-6 level in vivo. In this study, we demonstrated that IL-6-induced Arid5a in T cells stabilized Stat3 mRNA by inhibiting the function of an RNAse Regnase-1, and thereby promoted the differentiation of Th17 cells. Thus, Arid5a contributes to elevation of IL-6 level in vivo, but also drives Th17 differentiation.

Research Products

• [Journal Article] Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA (2016)
  • Author(s): Masuda, K., Ripley, B., Nyati, K., Dubey, P., Zaman, M., Hanieh, H., Hoga, M., Yamashita, K., Standley, D., Mashima, T., Katahira, M., Okamoto, T., Matsuura, Y., Takeuchi, O. and Kishimoto, T.
  • Journal Title: Journal of Experimental Medicine Volume: 213 Issue: 4 Pages: 605-619
  • DOI: 10.1084/jem.20151289
  • Peer Reviewed / Open Access
• [Presentation] T-cell intrinsic role of Arid5a as a stability protein of Stat3 mRNA in an IL-6-dependent manner (2015)
  • Author(s): Kazuya Masuda, Barry Ripley, Kishan Kumar Nyati, Praveen Kumar Dubey, Mohammad Mahabub-Uz Zaman and Tadamitsu Kishimoto
  • Organizer: The 44th Annual Meeting of The Japanese society for Immunology
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Patent(Industrial Property Rights)] 新規な敗血症治療剤及び/又はそのスクリーニング方法 (2015)
  • Inventor(s): 岸本忠三、増田和哉、中外製薬
  • Industrial Property Rights Holder: 岸本忠三、増田和哉、中外製薬
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-04-16
  • Overseas
• [Patent(Industrial Property Rights)] 新規な肺疾患治療剤及び/又はそのスクリーニング方法 (2015)
  • Inventor(s): 岸本忠三、増田和哉、中外製薬
  • Industrial Property Rights Holder: 岸本忠三、増田和哉、中外製薬
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-06-30
  • Overseas