Analysis of Bach2-mediated regulation of the chronic allergic inflammation

• Project/Area Number: 26293069
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• 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): KUWAHARA Makoto 愛媛大学, 大学院医学系研究科, 助教 (00568214) ; TAMAUCHI Hidekazu 愛媛県立医療大学, 保健科学部, 教授 (60188414)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: Bach2 / Batf / Th2 / Th2型気道炎症 / アレルギー炎症 / mTORC1 / Akt / アレルギー / 免疫学 / 炎症 / 免疫

Outline of Final Research Achievements

The expression of Bach2, a transcriptional repressor, in CD4 T cells is reduced by antigenic stimulation. The decreased Bach2 expression is resulted in the onset of Th2-type allergic airway inflammation. However, molecular mechanism by which Bach2 regulates Th2-type airway inflammation. In this study, we found that Bach2 interacts with Batf family transcription factors and binds to the AP-1 consensus DNA motifs at the locus control region of the Th2 cytokine gene locus. Thus, Bach2-Batf complex inhibits Th2 cell differentiation and subsequent Th2-type airway inflammation.

Research Products

• [Int'l Joint Research] NIAID(米国)
• [Journal Article] Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop. (2016)
  • Author(s): Kuwahara M, Ise W, Ochi M, Suzuki J, Kometani K, Maruyama S, Izumoto M, Matsumoto A, Takemori N, Takemori A, Shinoda K, Nakayama T, Ohara O, Yasukawa M, Sawasaki T, Kurosaki T, Yamashita M.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 12596-12596
  • DOI: 10.1038/ncomms12596
  • Peer Reviewed / Open Access
• [Journal Article] Gfi1, a transcriptional repressor, inhibits the induction of the T helper type 1 programme in activated CD4 T cells (2016)
  • Author(s): Junpei Suzuki, Saho Maruyama, Hidekazu Tamauchi, Makoto Kuwahara, Mika Horiuchi, Masumi Mizuki, Mizuki Ochi, Tatsuya Sawasaki, Jinfang Zhu, Masaki Yasukawa, Masakatsu Yamashita
  • Journal Title: Immunology Volume: 147 Issue: 4 Pages: 476-487
  • DOI: 10.1111/imm.12580
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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
• [Presentation] Bach2 interacts with Batf family transcription factors and inhibits Th2 cell differentiation. (2016)
  • Author(s): Ochi M., Kuwahara M., Suzuki J., Matsumoto A., Kurosaki T., Yasukawa M., Sawasaki T., Yamashita M.
  • Organizer: International Conference of Immunology 2016
  • Place of Presentation: メルボルン、オーストラリア
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Bach2 controls the thpe-2 immune response by regulating glutamine metabolism (2015)
  • Author(s): KUWAHARA Makoto, OCHI Mizuki, IZUMOTO Maya, KUROSAKI Tomohiro, YAMASHITA Masakatsu
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市)
  • Year and Date: 2015-11-18
• [Presentation] Bach2 and Blimp1 cooperatively regulate Il1rl1 expression in CD4 T cells (2015)
  • Author(s): IZUMOTO Maya, KUWAHARA Makoto, OCHI Mizuki, MATSUMOTO Akira, YAMASHITA Masakatsu
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市)
  • Year and Date: 2015-11-18
• [Presentation] Bach2 interacts with Batf family transcription factors and inhibits Th2 cell differentiation (2015)
  • Author(s): OCHI Mizuki, KUWAHARA makoto, MATSUMOTO Akira, KUROSAKI Tomohiro, YAMASHITA Masakatsu
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市)
  • Year and Date: 2015-11-18
• [Presentation] Bach2 inhibits Th2-type immune responses by regulating glutamine metabolism (2015)
  • Author(s): Masakatsu Ymasahita, Makoto Kuwahara
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京都港区)
  • Year and Date: 2015-05-26
• [Presentation] Th2細胞分化には細胞内グルタミン代謝が必要である (2015)
  • Author(s): 塩入幹汰、桑原誠、山下政克
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京都港区)
  • Year and Date: 2015-05-26
• [Presentation] Bach2 controls Th2 cell-mediated immune responses through regulation of glutaminolysis (2014)
  • Author(s): Kuwahara M, Ochi M, Kiyoi T, Kurosaki T 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] Bach2-Blimp1 axis plays an important role in the regulation of allergic airway inflammation (2014)
  • Author(s): Izumoto M, Kuwahara M, Kiyoi T, Shinoda K, Nakayama T, Kurosaki T 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] Th2細胞分化におけるグルタミン代謝の役割とBach2による制御 (2014)
  • Author(s): 山下政克
  • Organizer: 第2回がんと代謝研究会
  • Place of Presentation: 東京理科大学葛飾キャンパス
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 転写調節因子Bach2によるヘルパーT細胞サブセット分子とアレルギー性気道炎症の制御 (2014)
  • Author(s): 桑原誠、山下政克
  • Organizer: 第24回 Kyoto T Cell Conference
  • Place of Presentation: 京都平安ホテル
  • Year and Date: 2014-05-16 – 2014-05-17
• [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
  • URL: http://ehime-u-immunology.com/index.html
• [Remarks] 愛媛大学大学院医学系研究科免疫学ホームページ
  • URL: http://ehime-u-immunology.com/