Dynamics of innate immune cells per se in autoimmune CNS disorders

• Project/Area Number: 17K09776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: KAWACHI Izumi 新潟大学, 医歯学系, 准教授 (40432083)
• Co-Investigator(Kenkyū-buntansha): 豊島 靖子 新潟大学, 脳研究所, 准教授 (20334675)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 視神経脊髄炎 / 多発性硬化症 / アストロサイト / 自然免疫 / マクロファージ

Outline of Final Research Achievements

Neuromyelitis optica (NMO) is an autoimmune CNS disorder, which is characterized by aquaporin-4 water channel (AQP4) autoantibodies. Based on our pathological study using autopsied samples from NMO cases, CNS lesions at initial/early active stages in NMO included some granulocytes, interleukin-17-producing T cells and macrophages. These data suggest that these cells might provide initial signals, which induce entry of AQP4 autoantibodies from the outside of CNS via blood-brain barrier, and contribute active CNS lesions in NMO.

Academic Significance and Societal Importance of the Research Achievements

視神経脊髄炎はアクアポリン4自己抗体と補体が関連する中枢神経系自己免疫疾患であり, 本邦に多い指定難病の一つである. 早期病変にTH17/TC17をはじめとした新たな炎症向性リンパ球・顆粒球と炎症向性マクロファージ・ミクログリアを新たに見出した. 同細胞を抑制する分子標的治療の開発に向けた病態基盤の一部を確立したという点で意義があると考えられる.

Research Products

• [Journal Article] Neuropathological features of “non‐motor” symptoms in multiple sclerosis and neuromyelitis optica (2019)
  • Author(s): Izumi Kawachi
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 10 Issue: 3 Pages: 161-168
  • DOI: 10.1111/cen3.12533
  • Peer Reviewed
• [Journal Article] 増大特集 Antibody Update 2018 傍腫瘍性神経症候群と自己抗体 (2018)
  • Author(s): 河内 泉
  • Journal Title: BRAIN and NERVE Volume: 70 Issue: 4 Pages: 329-339
  • DOI: 10.11477/mf.1416201006
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2018-04-01
• [Journal Article] 多発性硬化症に自己抗体の関与はあるか (2018)
  • Author(s): 河内泉
  • Journal Title: Clinical Neuroscience Volume: 36 Pages: 1286-1290
• [Presentation] Characteristic features of longitudinal cognitive function in a Japanese cohort of MS (2019)
  • Author(s): Izumi Kawachi, Takahiro Wakasugi, Etsuji Saji, Fumihiro Yanagimura, Kaori Yanagawa, and Osamu Onodera
  • Organizer: 8th Annual Meeting of the International MS Cognition Society (IMSCOGS)
  • Int'l Joint Research
• [Presentation] Characterization of inflammatory axis of CNS lesions in neuromyelitis optica spectrum disorders (2019)
  • Author(s): Yanagimura F., Saji E., Wakasugi T., Hokari M., Toyoshima Y., Nakajima T., Takahashi H., Kakita A., Nishizawa M., Onodera O., Kawachi I.
  • Organizer: The 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
  • Int'l Joint Research
• [Presentation] 神経学と免疫学のクロストークから読み解く神経疾患 － 多発性硬化症から認知症まで (2019)
  • Author(s): Izumi Kawachi
  • Organizer: NEUARO 2019, 第42回日本神経科学大会, 第62回日本神経化学会大会
  • Int'l Joint Research / Invited
• [Presentation] Cross-interaction of neuro-immune axis in multiple sclerosis (2018)
  • Author(s): Izumi Kawachi
  • Organizer: 日本神経学会
  • Invited
• [Presentation] ouble inversion recovery imaging MRI: A good tool to identify optic neuritis lesions in multiple sclerosis and neuromyelitis optica (2018)
  • Author(s): Izumi Kawachi, Etsuji Saji, Mariko Hokari, Akiko Yokoseki, Takahiro Wakasugi, Fumihiro Yanagimura, and Osamu Onodera
  • Organizer: The 70th. Annual meeting of the American Academy of Neurology
  • Int'l Joint Research
• [Presentation] Up-to-date pathology in NMO (2018)
  • Author(s): Izumi Kawachi
  • Organizer: 19th International Congress of Neuropathology (ICN2018)
  • Int'l Joint Research / Invited
• [Presentation] Radiological, immunological, and pathological analysis of ependymal cells in neuromyelitis spectrum disorders (2018)
  • Author(s): Fumihiro Yanagimura, Etsuji Saji, Takahiro Wakasugi, Yasuko Toyoshima, Akiyoshi Kakita, Hitoshi Takahashi, Osamu Onodera, Izumi Kawachi
  • Organizer: 19th International Congress of Neuropathology (ICN2018)
  • Int'l Joint Research
• [Presentation] Dynamics of tissue regulatory T cells in Neuromyelitis optica spectrum disorders lesions (2017)
  • Author(s): Fumihiro Yanagimura, Etsuji Saji, Takahiro Wakasugi, Mariko Hokari, Yasuko Toyoshima, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa, Osamu Onodera, Izumi Kawachi
  • Organizer: The 33nd Congress of The European Committee for Treatment and Research in Multiple Sclerosis
  • Int'l Joint Research
• [Presentation] Double inversion recovery MRI in the evaluation of the anterior visual pathway in patients with multiple sclerosis and neuromyelitis optica spectrum disorders (2017)
  • Author(s): Etsuji Saji, Mariko Hokari, Akiko Yokoseki, Takahiro Wakasugi, Fumihiro Yanagimura, Kaori Yanagawa, Masatoyo Nishizawa, Osamu Onodera, and Izumi Kawachi
  • Organizer: The 33nd Congress of The European Committee for Treatment and Research in Multiple Sclerosis
  • Int'l Joint Research
• [Presentation] Current topics of myelin biology and beyond: Up-to-date knowledge on pathomechanism of MS and related disorders (2017)
  • Author(s): Izumi Kawachi, Masatoyo Nishizawa, Osamu Onodera
  • Organizer: 第60回神経化学会大会
  • Invited