Elucidation of regulation of intestinal macrophage differentiation from intracellular energy metabolism

• Project/Area Number: 15K15296
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kyorin University
• Principal Investigator: HISAMATSU TADAKAZU 杏林大学, 医学部, 教授 (60255437)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マクロファージ / 細胞内エネルギー代謝 / サイトカイン産生 / 代謝 / サイトカイン / 解糖系 / 酸化的リン酸化 / 分化 / エネルギー代謝 / IL-10 / 炎症性サイトカイン

Outline of Final Research Achievements

Macrophages are classified into M1 type that produces inflammatory cytokines, and M2 typeproducing IL-10 that acts on homeostasis and tissue repair. Regarding intracellular energy metabolism, aerobic glycolysis was mainly used in M1 type, and oxidative phosphorylation was mainly used in M2 type.
We clarified that the glycolysis system in the differentiation process is important for obtaining IL-10 productivity of M2-type macrophages. In addition, it was revealed that in the differentiated M2 type macrophages, in addition to the oxidative phosphorylation pathway conventionally mentioned, the glycolytic - ERK pathway was also used for cytokine production under LPS stimulation.

Research Products

• [Journal Article] Glycolysis regulates LPS-induced cytokine production in M2 polarized human macrophages. (2017)
  • Author(s): Chiba S, Hisamatsu T, Suzuki H, Mori K, Kitazume MT, Shimamura K, Mizuno S, Nakamoto N, Matsuoka K, Naganuma M, Kanai T.
  • Journal Title: Immunol Lett. Volume: Mar;183 Pages: 17-23
  • DOI: 10.1016/j.imlet.2017.01.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glycolytic pathway affects differentiation of human monocytes to regulatory macrophages. (2016)
  • Author(s): Suzuki H, Hisamatsu T, Chiba S, Mori K, Kitazume MT, Shimamura K, Nakamoto N, Matsuoka K, Ebinuma H, Naganuma M, Kanai T.
  • Journal Title: Immunol Lett. Volume: Aug;176 Pages: 18-27
  • DOI: 10.1016/j.imlet.2016.05.009
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Glycolytic pathway affects differentiation of human monocytes to regulatory macrophages (2016)
  • Author(s): 千葉明子、鈴木宏明、久松理一、中本伸宏、金井隆典
  • Organizer: 第45回日本免疫学会
  • Place of Presentation: 那覇
  • Year and Date: 2016-12-05
• [Presentation] ヒト抑制性マクロファージにおいて、LPS刺激によるIL-6産生には嫌気的解糖系が利用されている (2016)
  • Author(s): 千葉明子、久松理一、森 清人、北爪美奈、島村克好、水野慎大、中本伸宏、松岡克善、海老沼浩利、長沼 誠、金井隆典
  • Organizer: 第70回日本栄養・食糧学会
  • Place of Presentation: 神戸
  • Year and Date: 2016-05-13
• [Presentation] 解糖系によるIL-10産生型抑制性マクロファージの分化制御 (2015)
  • Author(s): 久松理一，鈴木宏明、千葉明子、森清人、島村克好、徳武美奈、 金井隆典
  • Organizer: 第52回消化器免疫学会総会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2015-07-30
• [Presentation] Glycolysis regulates macrophage differentiation into IL-10 producing phenotype (2015)
  • Author(s): H. Suzuki, T. Hisamatsu, M. Naganuma, H. Ebinuma, N. Nakamoto, K. Mori, M. Kitazume, K. Shimamura, S. Chiba, T. Kanai
  • Organizer: IMMUNOLOGY 2015, the American Association of Immunologist
  • Place of Presentation: ニューオーリンズ、米国
  • Year and Date: 2015-05-08
  • Int'l Joint Research