A novel function of Interferon regulatory factor-1

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659475
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Institute of Physical and Chemical Research (2013); Kanazawa Medical University (2012)
• Principal Investigator: ASANO Yoshihiro 独立行政法人理化学研究所, 統合生命医科学研究センター, 客員研究員 (70114353)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Saho 愛媛大学, 医学系研究科, 助教 (10301326)
• Co-Investigator(Renkei-kenkyūsha): TOMOSUGI Naohisa 金沢医科大学, 総合医学研究所, 教授 (80155580)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: アレルギー / 転写因子IRF-1 / IL-4 / Th2免疫応答

Research Abstract

We focused on the role of IRF-1 during a pathogen infection, especially the involvement of IRF-1 in the suppression of Th2 during the pathogen infection. We found that IRF-1 directly suppresses the transcription of Il4 gene of Th2 cells. IRF-1 binds to the silencer region of Il4 gene by the influence of soluble factor that produced by Listeria-infected APCs and down-regulates the Il4 gene transcription. We identified that IL-1 mediates the activity of the soluble factor. According to the results presented, we propose that IRF-1 functions to induce the Th1 shift via two distinct mechanisms, the previously known mechanism and a novel function described here. IRF-1 activates the Il12 p40 gene promoter activity and induces the gene transcription, resulted in the shift to Th1 subset. In addition, IRF-1 acts on the silencer region of Il4 gene by the influence of IL-1 and inhibits the transcription of the Il4 gene in Th2 cells.

Research Products

• [Journal Article] The Menin-Bach2 axis is critical for regulating CD4 T-cell senescence and cytokine homeostasis (2014)
  • Author(s): M. Kuwahara, J. Suzuki, S. Tofukuji, T. Yamada, M. Kanoh, A. Matsumoto, S. Maruyama, K. Kometani, T. Kurosaki, O. Ohara, T. Nakayama, M. Yamashita
  • Journal Title: Nat. Commun
  • DOI: 10.1038/ncomms4555
• [Journal Article] Listeria infection inhibits IgE production in regional lymphonodes by suppressing chemotaxis of basophils to lymph nodes (2013)
  • Author(s): M. Kanoh, S. Maruyama, Y. Asano
  • Journal Title: Microbiol. Immunol Volume: 57 Pages: 842-848
• [Journal Article] Autophagic control of Listeria determines the infection-induced death of macrophages (2013)
  • Author(s): Matsumoto, S.Maruyama, S. Takahashi, Y. Miyoshi, M. Kanoh, M. Kuwahara, T. Yamada, M. Yamashiita, Y. Asano
  • Journal Title: J Vaccine Immunotechnology Volume: 1 Pages: 6-11
• [Presentation] A novel function of Interferon regulatory factor-1 to inhibit Th2 cells by silencing Il4 gene during Listeria infection (2013)
  • Author(s): S. Maruyama, M. Kanoh, A. Matsumoto, M. Yamashita, Y. Asano
  • Organizer: JSI Annual Meeting
  • Place of Presentation: Chiba
  • Year and Date: 20131211-13
• [Book] Th2細胞におけるIL-4遺伝子発現のIRF-1による制御---Th1/Th2バランス調節におけるIRF-1の新しい役割 (2013)
  • Author(s): 丸山砂穂、浅野喜博
  • Total Pages: 18-24
  • Publisher: 臨床免疫・アレルギー科