The study to clarify the molecular mechanism of fate decision of activated CD4 T cells

• Project/Area Number: 25670232
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Ehime University
• Principal Investigator: YAMASHITA Masakatsu 愛媛大学, 医学(系)研究科(研究院), 教授 (00311605)
• Co-Investigator(Renkei-kenkyūsha): OHARA Osamu 公益財団法人かずさDNA研究所, 副所長 (20370926)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 免疫 / T細胞 / 分化 / 老化 / 記憶 / 免疫学 / Bach2 / アレルギー / T細胞免疫記憶

Outline of Final Research Achievements

In this study, we found that Menin plays a critical role in the fate decision of activated T cells. Menin was required for the memory CD4 and CD8 T cell generation. Furthermore, TCR/IL-2-mediated activation of Menin-deficient T cells in vitro resulted in the premature cellular senescence. Menin-deficient naive CD4 T cells preferentially differentiated into Th1 and Th2 cells in vitro, whereas Th17 cell differentiation was impaired. The phenotypes observed in the Menin-deficient T cells were partially mediated by the reduced expression of Bach2. Therefore, the Menin-Bach2 pathway plays an important role in the regulation T cell-mediated immune responses.

Research Products

• [Journal Article] The Menin-Bach2 axis is critical for regulating CD4 T cell senescence and cytokine homeostasis (2014)
  • Author(s): Kuwahara, M., Suzuki, J., Tofukuji, S., Yamada, T., Kanoh, M., Matsumoto, A., Maruyama, S., Kometani, K., Kurosaki, T., Ohara, O., Nakayama, T., Yamashita, M
  • Journal Title: Nature Comm Volume: 5 Issue: 1 Pages: 3555-3555
  • DOI: 10.1038/ncomms4555
  • Peer Reviewed / Open Access
• [Journal Article] A novel small compound SH-2251 suppresses Th2 cell-dependent airway inflammation through selective modulation of chromatin status at the Il5 gene locus (2013)
  • Author(s): Suzuki J, Kuwahara M, Tofukuji S, Imamura M, Kato F, Nakayama T, Ohara O, Yamashita M
  • Journal Title: PLoS ONE Volume: 8 Issue: 4 Pages: e61785-e61785
  • DOI: 10.1371/journal.pone.0061785
  • Peer Reviewed
• [Presentation] Menin plays a critical role in the expansion and maintenance of antigen-specific CD8+ T cells upon infection. (2014)
  • Author(s): Yamada T, Kano M, Matsumoto A, Yasuoka T, Suzuki J, Kuwahara M and Yamashita M.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Crucial role of Menin in the epigenetic regulation of Satb1 expression in CD8 T cells. (2014)
  • Author(s): Suzuki J, Yamada T, Yasuoka T, Ochi M, Kuwahara M, Yasukawa M and Yamashita M.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Menin inhibits transcriptional programs that promote CD4 T cell senescence (2013)
  • Author(s): Kuwahara M, Yamada T, Nakayama T, Yamashita M.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ
• [Presentation] Crucial role of Menin in the regulation of CD4 T cell terminal differentiation and senescence (2013)
  • Author(s): Kuwahara M, Nakayama T, Yamashita M.
  • Organizer: Th 6th International Workshop of Kyoto T cell Conference
  • Place of Presentation: 京都大学
• [Remarks] 愛媛大学大学院医学系研究科免疫学・感染防御学ホームページホームページ
  • URL: http://www.m.ehime-u.ac.jp/school/immunology/
• [Remarks] 愛媛大学大学院医学系研究科免疫学・感染防御学
  • URL: http://www.m.ehime-u.ac.jp/school/immunology/