The role of midkine family in inflammatory demyelination

• Project/Area Number: 18590933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: MIZUNO Tetsuya Nagoya University, 環境医学研究所, 准教授 (70335008)
• Co-Investigator(Kenkyū-buntansha): 錫村 明生 名古屋大学, 環境医学研究所, 教授 (50196896)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: ミッドカイン / 炎症性脱髄 / 調節性T細胞 / 脳神経疾患 / 神経免疫

Research Abstract

多発性硬化症、自己免疫性脳脊髄炎などの炎症性脱髄において、ミッドカインが、自己免疫を調節している調節性T細胞や調節性樹状細胞の機能を抑制することによりその発症に関与していることを明らかにした.さらに、抗体よりも優れた結合力と特異性をもつRNAアプタマーを用いたミッドカイン機能の制御によって、自己免疫性脳脊髄炎の発症を効果的に抑制することができた.本研究は、ミッドカイン抑制を標的とした炎症性脱髄疾患の新規治療法の可能性を示すものである.

Research Products

• [Journal Article] Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity (2008)
  • Author(s): Liang J, Mizuno T, Suzumura A 他(11人10番目)
  • Journal Title: Brain Research 1210 Pages: 11-19
  • Peer Reviewed
• [Journal Article] Microglia express a functional receptor for interleukin-23 (2008)
  • Author(s): Sonobe Y, Mizuno T, Suzumura A 他(7人6番目)
  • Journal Title: Biochemical and Biophysical Research Communications 370 Pages: 129-133
  • Peer Reviewed
• [Journal Article] Interferon-. directly induces neurotoxicity through a neuron specific, calcium- permeable complex of IFN- receptor and AMPA GluR1 receptor (2008)
  • Author(s): Mizuno T, Suzumura A 他(10人1番目)
  • Journal Title: FASEB Journal 22 Pages: 1797-1806
  • Peer Reviewed
• [Journal Article] Production and functions of IL-17 in microglia (2008)
  • Author(s): Kawanokuchi J, Mizuno T, Suzumura A 他(7人5番目)
  • Journal Title: Journal of Neuroimmunology 194 Pages: 54-61
  • Peer Reviewed
• [Journal Article] Inhibition of midkine alleviates experimental autoimmune encephalo- myelitis through the expansion of regulatory T cell population (2008)
  • Author(s): Wang J, Takeuchi H, Sonobe Y, Mizuno T 他(12人5番目)
  • Journal Title: Proc Natl Acad Sci U S A 105 Pages: 3915-3920
  • Peer Reviewed
• [Journal Article] Interferon-γ directly induces neurotoxicity through a neuron specific, calciumpermeable complex of IFN-γ receptor and AMPA GluR1 receptor. (2008)
  • Author(s): MIZUNO Tetsuya, SUZUMURA Akio
  • Journal Title: FASEB Journal 22 Pages: 1797-1806
  • Peer Reviewed
• [Journal Article] Microglia express a functional receptor for interleukin-23. (2008)
  • Author(s): SONOBE Yoshifumi, MIZUNO Tetsuya, SUZUMURA Akio
  • Journal Title: Biochemical and Biophysical Research Communic ations. 370 Pages: 129-133
  • Peer Reviewed
• [Journal Article] Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity. (2008)
  • Author(s): LIANG Jianfeng, MIZUNO Tetsuya, SUZUMURA Akio
  • Journal Title: Brain Research 1210 Pages: 11-19
  • Peer Reviewed
• [Journal Article] Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell (2008)
  • Author(s): Wang J, Takeuchi H. Sonobe Y. Mizuno T.
  • Journal Title: Proceedings of the National Academy of Sciences USA 105 Pages: 3915-3920
  • Peer Reviewed
• [Journal Article] Production and functions of IL-17 in microglia. (2008)
  • Author(s): Kawanokuchi J, Mizuno T, Suzumura A,
  • Journal Title: Journal of Neuroimmunology 194 Pages: 54-61
  • Peer Reviewed
• [Journal Article] Chronological changes of CD4+ and CD8+ T cell subsets in the experimental autoimmune encephalo- myelitis, a mouse model of multiple sclerosis (2007)
  • Author(s): Sonobe Y, Jin S, Takeuchi H, Mizuno T 他(7人6番目)
  • Journal Title: Tohoku Journal of Experimental Medicine 213 Pages: 329-339
  • Peer Reviewed
• [Journal Article] Chronological changes of CD8-T cell subsets in the cxperimental auloimmune eneephalomvelilis, a mouse model of multiple (2007)
  • Author(s): Sonobe Y, Jin S, Takeuchi H, Mizuno T,
  • Journal Title: Tohoku Journal of Experimental Medicine 213 Pages: 329-339
  • Peer Reviewed
• [Journal Article] Role of glia-derived cytokines on neuronal degeneration and regeneration (2006)
  • Author(s): Suzumura A, Takeuchi H, Zhang G, Kuno R, Mizuno T
  • Journal Title: Annals of New York Academy of Science 1088 Pages: 219-229
  • Peer Reviewed
• [Journal Article] Production of interferon- (2006)
  • Author(s): Kawanokuchi J, Mizuno T, Takeuchi H, Kato H, Wang J, Mitsuma N, Suzumura A
  • Journal Title: by microglia Multiple Sclerosis 12 Pages: 558-564
  • Peer Reviewed
• [Journal Article] Role of glia-derived cytokines on neuronal degeneration and regeneration. (2006)
  • Author(s): Suzumura A, Takeuchi H, Zhang G, Kuno R, Mizuno T
  • Journal Title: Annals of New York Academy of Science 1088 Pages: 219-229
• [Journal Article] Midkine deficiency protects against Experimental Autoimmnue Encephalomyelitis by expansion of CD4^+CD25^+Foxp3^+ regulatory T cells. (2006)
  • Author(s): Wwng J, Takeuchi H, Jin S, Sonobe Y, Mizuno T, Muramatsu H, Muramatsu T, Suzumura A
  • Journal Title: Journal of Neuroimmunology 178 Pages: 169-169
• [Journal Article] Production of interferon-γby microglia. (2006)
  • Author(s): Kawanokuchi J, Mizuno T, Takeuchi H, Kato H, Wang J, Mitsuma N, Suzumura A
  • Journal Title: Multiple Sclerosis 12 Pages: 558-564
• [Presentation] 中枢神経系におけるインターロイキン-25の発現とその機能 (2008)
  • Author(s): 片岡邦夫、水野哲也、錫村明生
  • Organizer: 第20回神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-17
• [Presentation] 中枢神経系におけるインクーロイキン-25の発現とその機能 (2008)
  • Author(s): 片岡邦夫, 水野哲也, 錫村明生
  • Organizer: 第20回神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-17
• [Presentation] 抗体及びaptamerを用いたMidkine阻害に基ずく多発性硬化症の新規治療法開発 (2007)
  • Author(s): 薗部佳史
  • Organizer: 第19回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2007-04-12
• [Presentation] 抗体及びaptamerを用いたMidkine阻害に基ずく多発性硬化症の新規治療法開発. (2007)
  • Author(s): 薗部佳史
  • Organizer: 第19回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2007-04-12
• [Presentation] Midkine欠損マウスでは制御性T細胞の増加によりEAEの発症が抑制される (2006)
  • Author(s): 竹内英之、王金岩、水野哲也、錫村明生
  • Organizer: 第47回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2006-05-11