Regulation of immune cell responses by heme

• Project/Area Number: 21249014
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: IGARASHI Kazuhiko 東北大学, 大学院・医学系研究科, 教授 (00250738)
• Co-Investigator(Kenkyū-buntansha): MOTOHASHI Hozumi 東北大学, 大学院・医学系研究科, 准教授 (00282351) ; MUTO Akihiko 東北大学, 大学院・医学系研究科, 准教授 (80343292) ; KATOH Yasutake 東北大学, 大学院・医学系研究科, 助教 (40397914) ; MURAYAMA Kazutaka 東北大学, 大学院・医工学研究科, 准教授 (40400452)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥48,230,000 (Direct Cost: ¥37,100,000、Indirect Cost: ¥11,130,000); Fiscal Year 2011: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000); Fiscal Year 2010: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000); Fiscal Year 2009: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
• Keywords: 遺伝子 / 免疫学 / 発生分化 / 蛋白質 / ストレス

Research Abstract

The transcription factor Bach2 is required in B cells for the antibody class switch DNA recombination and somatic hypermutation. In this project, we have established that the prosthetic group heme binds directly to Bach2 to inhibits its DNA binding activity and to induce rapid turnover within cells. We also identified a domain-like structure within Bach2 that mediates the regulation by heme. Three cysteine residues within this domain were critical for the heme-Bach2 interaction. These results suggest that heme functions as a signaling molecule in B cells to regulate immune responses.

Research Products

• [Journal Article] Heme regulates B cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2 (2011)
  • Author(s): Watanabe-Matsui, M., Muto, A., Matsui, T., Itoh-Nakadai, A., Nakajima, O., Murayama, K., Yamamoto, M., Ikeda-Saito, M., Igarashi, K.
  • Journal Title: Blood Volume: 117巻 Pages: 5438-5448
  • Peer Reviewed
• [Journal Article] Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch (2010)
  • Author(s): Muto, A., Ochiai, K., Kimura, Y., Itoh-Nakadai, A., Calame, K. L., Ikebe, D., Tashiro, S. and Igarashi, K.
  • Journal Title: EMBO J. Volume: 29巻 Pages: 4048-4061
  • Peer Reviewed
• [Journal Article] Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch (2010)
  • Author(s): Muto, A., Ochiai, K., Kimura, Y., Itoh-Nakadai, A., Calame, K.L., Ikebe, D., Tashiro, S., Igarashi, K.
  • Journal Title: EMBO J Volume: 29 Pages: 4048-4061
  • Peer Reviewed
• [Presentation] 鉄代謝と転写制御のクロストークとその出力異常 (2011)
  • Author(s): 五十嵐和彦
  • Organizer: 第12回WAKOつくばフォーラム
  • Place of Presentation: 筑波和光ホール
  • Year and Date: 2011-11-29
• [Presentation] 鉄代謝と転写制御のクロストークとその出力異常 (2011)
  • Author(s): 五十嵐和彦
  • Organizer: 第12回WAKOつくばフォーラム
  • Place of Presentation: 筑波和光ホール(茨城県つくば市)
  • Year and Date: 2011-11-29
• [Presentation] Regulation of erythroid and lympohoid differentiation by heme-binding transcription factors Bach1 and Bach2 (2010)
  • Author(s): K.Igarashi
  • Organizer: 日本血液学会シンポジウム
  • Place of Presentation: 横浜市
  • Year and Date: 2010-09-25
• [Presentation] Regulation of erythroid and lympohoid differentiation by heme-binding transcription factors Bach1 and Bach2 (2009)
  • Author(s): K. Igarashi
  • Organizer: 日本血液学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Dense co-regulators network for HO-1 gene expression 6th International Congress on Heme oxygenases (2009)
  • Author(s): 五十嵐和彦
  • Organizer: Heme oxygenases in Biology & Medicine
  • Place of Presentation: マイアミビーチリゾートアンドスパ
  • Year and Date: 2009-10-01
• [Presentation] Dense co-regulators network for HO-1 gene expression 6th International Congress on Heme oxygenases (2009)
  • Author(s): 五十嵐和彦
  • Organizer: Heme oxygenases in Biology & Medicine
  • Place of Presentation: マイアミビーチリゾートアンドスパ(米国)
  • Year and Date: 2009-10-01
• [Book] 遺伝情報の発現制御～転写機構からエピジェネェティクスまで～ (2012)
  • Author(s): 五十嵐和彦、深水昭吉、山本雅之
  • Total Pages: 429
  • Publisher: メディカルサイエンスインターナショナル
• [Remarks]
  • URL: http://www.biochem.med.tohoku.ac.jp
• [Remarks] 研究室HP
  • URL: http://www.biochem.med.tohoku.ac.jp/
• [Remarks]
  • URL: http://www.med.tohoku.ac.jp/org/medical/05/