Harmine regulates immune responses

• Project/Area Number: 25670233
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Research Institute, International Medical Center of Japan (2014); Keio University (2013)
• Principal Investigator: KIMURA Akihiro 独立行政法人国立国際医療研究センター, その他部局等, その他 (20533318)
• 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: ハルミン / LPS / Th17 / Treg / アルカロイド / Th17細胞 / Treg細胞 / IL-6 / マクロファージ

Outline of Final Research Achievements

Harmine suppresses LPS-induced IL-6 production. Target X for harmine is required for the inhibition by harmine on IL-6 production. Furthermore, we found that harmine suppresses LPS-induced endotoxin shock.
While Harmine enhances the development of Treg cells, it inhibits Th17 cell differentiation. We demonstrated that Target X for harmine is required for enhancement of Treg cells and suppression of Th17 cells. These results indicate that harmine regulates the immune responses via the Target X for harmine.

Research Products

• [Journal Article] ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells. (2015)
  • Author(s): Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, Kimura A, Sasaki K, Yasukawa H, Yoshimura A.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 112 Issue: 1 Pages: 160-165
  • DOI: 10.1073/pnas.1413234112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production (2014)
  • Author(s): Kimura A, Abe H, Tsuruta S, Chiba S, Fujii-Kuriyama Y, Sekiya T, Morita R, Yoshimura A.
  • Journal Title: Int Immunol. Volume: 26 Issue: 4 Pages: 209-220
  • DOI: 10.1093/intimm/dxt067
  • Peer Reviewed / Open Access
• [Journal Article] Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-Y expression and inducing IL-22 (2014)
  • Author(s): Abe H, Kimura A, Tsuruta S, Fukaya T, Sakaguchi R, et al.
  • Journal Title: Int Immunol. Volume: 26 Issue: 3 Pages: 129-137
  • DOI: 10.1093/intimm/dxt049
  • Peer Reviewed / Open Access
• [Journal Article] Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. (2013)
  • Author(s): Sekiya T, Kashiwagi I, Yoshida R, Fukaya T, et al.
  • Journal Title: Nat Immunol. Volume: 14 Issue: 3 Pages: 230-237
  • DOI: 10.1038/ni.2520
  • Peer Reviewed
• [Journal Article] IL-23-Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization (2013)
  • Author(s): Hasegawa E
  • Journal Title: J Immunol Volume: 190 Issue: 4 Pages: 1778-1787
  • DOI: 10.4049/jimmunol.1202495
  • Peer Reviewed
• [Journal Article] Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo. (2012)
  • Author(s): Yoshida R
  • Journal Title: Biochem Biophys Res Commun. Volume: 423 Issue: 2 Pages: 247-252
  • DOI: 10.1016/j.bbrc.2012.05.097
  • Peer Reviewed
• [Presentation] Aryl hydrocarbon receptor controls autoimmunity through regulating the development of regulatory B cells. (2013)
  • Author(s): 木村彰宏
  • Organizer: 第４２回日本免疫学会総会
  • Place of Presentation: 幕張メッセ、千葉
• [Patent(Industrial Property Rights)] ＩＬ－１０産生誘発ＡｈＲリガンドのスクリーニング方法 (2013)
  • Inventor(s): 木村彰宏、吉村昭彦
  • Industrial Property Rights Holder: 学校法人慶應義塾
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-233833
  • Filing Date: 2013-11-12