Analysis of innate immune cells in inflammatory demyelinating diseases of the central nervous system

• Project/Area Number: 23591236
• 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, 医歯学総合病院, 助教 (40432083)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Yasuko 新潟大学, 脳研究所, 准教授 (20334675)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 視神経脊髄炎 / 多発性硬化症 / 自然免疫機構 / アクアポリン4水チャネル / 神経免疫病態学 / I型インターフェロン / アクアポリン4 / 自然免疫

Research Abstract

Neuromyelitis optica (NMO) and multiple sclerosis are the two main autoimmune, inflammatory and demyelinating syndromes of the central nervous system. The discovery of NMO immunoglobulin G autoantibody, which targets the water channel aquaporin-4 (AQP4) and is a specific marker of NMO, should revolutionize understanding of pathogenesis in the two diseases. Not only IL-17/IFN-gamma-producing cells, but also innate immune cells including neutrophils, antigen-presenting cells, plasma cells and plasmablasts were evident in NMO lesions. These data suggest that unique dynamics of innate immune cells might be present in NMO in situ.

Research Products

• [Journal Article] Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody. (2014)
  • Author(s): Yokoseki A, Saji E, Arakawa M, Kosaka T, Hokari M, Toyoshima Y, Okamoto K, Takeda S, Sanpei K, Kikuchi H, Hirohata S, Akazawa K, Kakita A, Takahashi H, Nishizawa M, and Kawachi I.
  • Journal Title: Brain Volume: 137(2) Issue: 2 Pages: 520-536
  • DOI: 10.1093/brain/awt314
  • Peer Reviewed
• [Journal Article] Gray matter involvement in multiple sclerosis and neuromyelitis optica. (2014)
  • Author(s): Kawachi I, Nishizawa M.
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 5(1) Issue: 1 Pages: 69-76
  • DOI: 10.1111/cen3.12077
  • Peer Reviewed
• [Journal Article] Apathy/depression, but not subjective fatigue, is related with cognitive dysfunction in patients with multiple sclerosis. (2014)
  • Author(s): Niino M, Mifune N, Kohriyama T, Mori M, Ohashi T, Kawachi I, Shimizu Y, Fukaura H, Nakashima I, Kusunoki S, Miyamoto K, Yoshida K, Kanda T, Nomura K, Yamamura T, Yoshii F, Kira J, Nakane S, Yokoyama K, Matsui M, Miyazaki Y, Kikuchi S.
  • Journal Title: BMC Neurology Volume: 14(1) Issue: 1 Pages: 1-8
  • DOI: 10.1186/1471-2377-14-3
  • Peer Reviewed
• [Journal Article] Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013)
  • Author(s): Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, et. al.
  • Journal Title: Lancet Neurology Volume: 12 Issue: 2 Pages: 157-165
  • DOI: 10.1016/s1474-4422(12)70310-1
  • Peer Reviewed
• [Journal Article] Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy. (2013)
  • Author(s): Yokoseki A, Saji E, Arakawa M, Hokari M, Ishiguro T, Yanagimura F, Ishihara T, Okamoto K, Nishizawa M, Kawachi I.
  • Journal Title: Multiple Sclerosis Journal Volume: 19(9) Issue: 9 Pages: 1230-1233
  • DOI: 10.1177/1352458513481395
  • Peer Reviewed
• [Journal Article] T lymphocytes: Helpers. (2013)
  • Author(s): Kawachi I, Kondo T.
  • Journal Title: ENCYCLOPEDIA OF LIFE SCIENCES Volume: eLS (Wiley Online Library) Pages: 1-13
  • DOI: 10.1002/9780470015902.a0001224.pub3
  • Peer Reviewed
• [Journal Article] Late-onset anti-NMDA receptor encephalitis. (2013)
  • Author(s): Titulaer MJ, McCracken L, Gabilondo I, Iizuka T, Kawachi I, Bataller L, Torrents A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J.
  • Journal Title: Neurology Volume: 81(12) Issue: 12 Pages: 1058-1063
  • DOI: 10.1212/wnl.0b013e3182a4a49c
  • Peer Reviewed
• [Journal Article] Efficacy of methylprednisolone pulse therapy for acute relapse in Japanese patients with multiple sclerosis and neuromyelitis optica: a multicenter retrospective analysis – 1. Whole group analysis (2013)
  • Author(s): 2. Kira J
  • Journal Title: Clin Exp Neuroimmunol Volume: 4 Issue: 3 Pages: 305-317
  • DOI: 10.1111/cen3.12071
  • Peer Reviewed
• [Journal Article] 多発性硬化症・視神経脊髄炎における認知機能障害.多発性硬化症の新展開 (2013)
  • Author(s): 河内泉,西澤正豊
  • Journal Title: 脳21 Volume: 16(4) Pages: 454-459
• [Journal Article] 視神経脊髄炎には認知機能障害と大脳皮質変性が存在する (2013)
  • Author(s): 河内泉
  • Journal Title: MS Frontier Volume: 2(2) Pages: 22-25
• [Journal Article] Dropped head syndrome in amyotrophic lateral sclerosis. (2013)
  • Author(s): Uemura M, Kosaka T, Shimohata T, Ishikawa M, Nishihira Y, Toyoshima Y, Yanagawa K, Kawachi I, Takahashi H, Nishizawa M
  • Journal Title: Amyotroph Lateral Scler Frontotemporal Degener Volume: 14 Issue: 3 Pages: 232-233
  • DOI: 10.3109/17482968.2012.727424
  • Peer Reviewed
• [Journal Article] T lymphocytes: Helpers (2013)
  • Author(s): Kawachi I, Kondo T
  • Journal Title: ENCYCLOPEDIA OF LIFE SCIENCES Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Cognitive impairment and cortical degeneration in neuromyelitis optica. (2012)
  • Author(s): Saji E, Arakawa M, Yanagawa K, Toyoshima Y, Yokoseki A, Okamoto K, Otsuki M, Akazawa K, Kakita A, Takahashi H, Nishizawa M, Kawachi I.
  • Journal Title: Ann Neurol. Volume: 73 Issue: 1 Pages: 65-76
  • DOI: 10.1002/ana.23721
  • Peer Reviewed
• [Journal Article] Chorea as the First Sign in a Patient with Elderly- Onset Systemic Lupus Erythematosus (2012)
  • Author(s): Y Ariizumi,et al.
  • Journal Title: Case Reports in Neurological Medicine Volume: in press Pages: 317082-317082
  • DOI: 10.1155/2012/317082
  • Peer Reviewed
• [Journal Article] Successful treatment of neuroborreliosis with combined administration of antibiotics and steroids : A case report (2012)
  • Author(s): Takado Y, Shimohata T, Kawachi I, Tanaka K, Nishizawa M
  • Journal Title: Rinsho Shinkeigaku Volume: 52(6) Pages: 411-5
  • NAID: 130004505269
  • Peer Reviewed
• [Journal Article] Neuromyelitis optica following thymectomy with severe spinal cord atrophy after frequent relapses for 30 years (2012)
  • Author(s): Hironishi M, Ishimoto S, Sawanishi T, Miwa H, Kawachi I, Kondo T
  • Journal Title: Brain Nerve Volume: 64(8) Pages: 951-5
  • Peer Reviewed
• [Journal Article] Semiquantitative measurement of aquaporin-4 antibodies as a possible surrogate marker of neuromyelitis optica spectrum disorders with systemic autoimmune diseases (2012)
  • Author(s): Katsumata Y, Kawachi I, Kawaguchi Y, Gono T, Ichida H, Hara M, Yamanaka H
  • Journal Title: Mod Rheumatol Volume: 22(5) Pages: 676-84
  • NAID: 10031027637
  • Peer Reviewed
• [Journal Article] Successful treatment of neuroborreliosis with combined administration of antibiotics and steroids: A case report (2012)
  • Author(s): Takado Y, Shimohata T, Kawachi I, Tanaka K, Nishizawa M
  • Journal Title: Rinsho Shinkeigaku Volume: 52 Pages: 411-415
  • NAID: 130004505269
  • Peer Reviewed
• [Journal Article] Chorea as the first sign in a patient with elderly-onset systemic lupus erythematosus. (2012)
  • Author(s): Ariizumi Y, Ozawa T, Tokutake T, Kawachi I, Hirose M, Katada S, Igarashi S, Tanaka K, Nishizawa M.
  • Journal Title: Case reports in neurological medicine Volume: 2012 Pages: 3-3
  • Peer Reviewed
• [Journal Article] A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans (2011)
  • Author(s): Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K
  • Journal Title: J Clin Invest Volume: 121 Pages: 4150-60
  • Peer Reviewed
• [Journal Article] A case of inflammatory myopathy with widely skin rash following use of supplements containing Spirulina (2011)
  • Author(s): Konno T, Umeda Y, Umeda M, Kawachi I, Oyake M, Fujita N
  • Journal Title: Rinsho Shinkeigaku Volume: 51 Pages: 330-3
  • NAID: 10031164014
  • Peer Reviewed
• [Journal Article] アクアポリン4抗体 (2011)
  • Author(s): 西澤正豊,河内泉
  • Journal Title: SRL宝函 Volume: 32(2) Pages: 4-12
• [Journal Article] A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans (2011)
  • Author(s): Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K.
  • Journal Title: J Clin Invest Volume: 121 Issue: 10 Pages: 4150-4160
  • DOI: 10.1172/jci58414
  • Peer Reviewed
• [Journal Article] Semiquantitative measurement of aquaporin-4 antibodies as a possible surrogate marker of neuromyelitis optica spectrum disorders with systemic autoimmune diseases. (2011)
  • Author(s): Katsumata Y, Kawachi I, Kawaguchi Y, Gono T, Ichida H, Hara M, Yamanaka H.
  • Journal Title: Mod Rheumatol Volume: Epub ahead of print Issue: 5 Pages: 676-684
  • DOI: 10.1007/s10165-011-0572-y
  • NAID: 10031027637
  • Peer Reviewed
• [Journal Article] A case of inflammatory myopathy with widely skin rash following use of supplements containing Spirulina. (2011)
  • Author(s): Konno T, Umeda Y, Umeda M, Kawachi I, Oyake M, Fujita N.
  • Journal Title: Rinsho Shinkeigaku. Volume: 51 Pages: 330-333
  • NAID: 10031164014
  • Peer Reviewed
• [Presentation] Optic Perineuritis-like Lesions in Neuromyelitis Optica : Radiological Assessments (2013)
  • Author(s): Yokoseki A, Saji E, Arakawa M, Hokari M, Nishizawa M, Kawachi I
  • Organizer: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2013-11-07
• [Presentation] Neuromyelitis Optica with Severe Progressive Cognitive and Psychiatric Impairment : Pathological Analysis of Three Autopsied Cases (2013)
  • Author(s): Arakawa M, Saji E, Toyoshima Y, Hokari M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • Organizer: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2013-11-07
• [Presentation] Radiological and Pathological Analyses of Cortical Lesions in Inflammatory Demyelinating Diseases of the Central Nervous System (2013)
  • Author(s): Saji E, Arakawa M, Yokoseki A, Hokari M, Toyoshima Y, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • Organizer: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2013-11-07
• [Presentation] Clinical Profiles of Elderly Patients with ADEM in A Japanese Cohort (2013)
  • Author(s): Hokari M, Saji E, Yokoseki A, Arakawa M, Nishizawa M, Kawachi I
  • Organizer: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2013-11-07
• [Presentation] Paraneoplastic Anti-NMDA Receptor Encephalitis Presenting With Neuromyelitis Optica-Like Relapses (2013)
  • Author(s): Yanagimura F, Kawachi I, Saji E, Hokari M, Yokoseki A, Arakawa M, Nishizawa M
  • Organizer: The 6th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2013-11-07
• [Presentation] Longitudinal flow cytometric profiles of immune cells in the cerebrospinal fluid and blood of patients with multiple sclerosis under fingolimod therapy (2013)
  • Author(s): Kawachi I, Yokoseki A, Saji E, Arakawa M, Hokari M, Nishizawa M
  • Organizer: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2013-10-04
• [Presentation] CNS pathology in neuromyelitis optica : region-dependent dynamics of aquaporin-4 (2013)
  • Author(s): Arakawa M, Saji E, Toyoshima Y, Hokari M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • Organizer: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2013-10-04
• [Presentation] Longitudinal flow cytometric profiles of immune cells in the cerebrospinal fluid and blood of patients with multiple sclerosis under fingolimod therapy. (2013)
  • Author(s): Kawachi I, Yokoseki A, Saji E, Arakawa M, Hokari M, Nishizawa M.
  • Organizer: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] CNS pathology in neuromyelitis optica: region-dependent dynamics of aquaporin-4. (2013)
  • Author(s): Arakawa M, Saji E, Toyoshima Y, Hokari M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I.
  • Organizer: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Copenhagen, Denmark
• [Presentation] Characteristic features of inflammatory demyelination and neurodegeneration in neuromyelitis optica spectrum disorder (2012)
  • Author(s): Arakawa M, Toyosima Y, Saji E, Yanagawa K, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • Organizer: The 11th International Congress of Neuroimmunology
  • Place of Presentation: Boston, USA
  • Year and Date: 2012-11-07
• [Presentation] Potential role of CCR6+ T cells in inflammatory demyelinating diseases of central nervous system (2012)
  • Author(s): Saji E, Arakawa M, Hokari M, Toyosima Y, Yanagawa K, Yokoseki A, Kakita A, Takahashi H, Nishizawa M, Kawachi I
  • Organizer: The 11th International Congress of Neuroimmunology
  • Place of Presentation: Boston, USA
  • Year and Date: 2012-11-06
• [Presentation] Diagnostic dilemma of Japanese patients with AQP4 antibody (2012)
  • Author(s): Kawachi I, Yanagawa K, Saji E, Yokoseki A, Hokari M, Nishizawa M
  • Organizer: The 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Lion, France
  • Year and Date: 2012-10-11
• [Presentation] Possible role of subarachnoid space as the initiating site for triggering the immune-mediated injury in CNS demyelinating diseases (2012)
  • Author(s): Kawachi I, Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Hokari M, Kakita A, Takahashi H, Nishizawa H
  • Organizer: The 5th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Beijing, China
  • Year and Date: 2012-09-15
• [Presentation] Characteristic features of cognitive dysfunction in neuromyelitis optica and multiple sclerosis (2012)
  • Author(s): Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Hokari M, Nishizawa M, and Kawachi I
  • Organizer: The 5th Congress of the Pan-Asia Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Beijing, China
  • Year and Date: 2012-09-14
• [Presentation] Diagnostic dilemma of Japanese patients with AQP4 antibody (2012)
  • Author(s): Kawachi I, Yanagawa K, Saji E, Yokoseki A, Hokari M, Nishizawa M
  • Organizer: The 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
  • Place of Presentation: Lion, France
• [Presentation] Humoral and cellular immune responses in neuromyelitis optica (2012)
  • Author(s): Kawachi I, Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Hokari M, Kakita A, Takahashi H, Nishizawa M
  • Organizer: The 5th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)
  • Place of Presentation: Beijing, China
  • Invited
• [Presentation] Absence of meningeal lymphoid neogenesis in neuromyelitis optica (2011)
  • Author(s): Kawachi I, Yanagawa K, Toyoshima Y, Saji E, Arakawa M, Yokoseki A, Kakita A, Takahashi H, Nishizawa M
  • Organizer: The 5th Joint Triennial Congress of the European and Americas Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Amsterdam, The Netherlands
  • Year and Date: 2011-10-21
• [Presentation] Possible association of retinal nerve fiber layer thinning with cognitive dysfunction in neuromyelitis optica (2011)
  • Author(s): Saji E, Yanagawa K, Toyoshima Y, Arakawa M, Yokoseki A, Nishizawa M, Kawachi I
  • Organizer: The 5th Joint Triennial Congress of the European and Americas Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Amsterdam, The Netherlands
  • Year and Date: 2011-10-21
• [Presentation] Absence of meningeal lymphoid neogenesis in neuromyelitis optica. (2011)
  • Author(s): Izumi Kawachi, Kaori Yanagawa, Yasuko Toyoshima, Etsuji Saji, Musashi Arakawa, Akiko Yokoseki, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa.
  • Organizer: 5th Joint Triennial Congress of the European and Americas Committee for Treatment and Research in Multiple Sclerosis.
  • Place of Presentation: アムステルダム (オランダ)
• [Presentation] Characteristic features of cognitive dysfunction in neuromyelitis optica. (2011)
  • Author(s): Etsuji Saji, Kaori Yanagawa, Yasuko Toyoshima, Musashi Arakawa, Akiko Yokoseki, Masatoyo Nishizawa, Izumi Kawachi.
  • Organizer: 5th Joint Triennial Congress of the European and Americas Committee for Treatment and Research in Multiple Sclerosis.
  • Place of Presentation: アムステルダム (オランダ)
• [Book] III.視神経脊髄炎の病態と治療. NMO spectrum disorder.アクチュアル脳・神経疾患の臨床.多発性硬化症と視神経脊髄炎 (2012)
  • Author(s): 河内泉,西澤正豊
  • Publisher: 中山書店.東京
• [Book] II. MSとNMOの基礎. 2.免疫制御のキープレイヤーとネットワーク.多発性硬化症(MS)と視神経脊髄炎(NMO)の基礎と臨床 (2012)
  • Author(s): 河内泉
  • Publisher: 医薬ジャーナル社.東京
• [Book] III.認知症をきたす疾患.多発性硬化症.アクチュアル脳・神経疾患の臨床.認知症神経心理学的アプローチ (2012)
  • Author(s): 河内泉,西澤正豊
  • Publisher: 中山書店.東京
• [Book] アクチュアル脳・神経疾患の臨床. III. 視神経脊髄炎の病態と治療. NMO spectrum disorder (2012)
  • Author(s): 河内泉, 西澤正豊
  • Publisher: 中山書店
• [Book] 多発性硬化症 (MS) と視神経脊髄炎 (NMO) の基礎と臨床. II. MSとNMOの基礎. 2. 免疫制御のキープレイヤーとネットワーク (2012)
  • Author(s): 河内泉
  • Publisher: 医薬ジャーナル社
• [Book] アクチュアル脳・神経疾患の臨床. III. 認知症をきたす疾患. 多発性硬化症. (2012)
  • Author(s): 河内泉
  • Publisher: 中山書店
• [Remarks] 新潟大学脳研究所神経内科学分野
  • URL: http://www.bri.niigata-u.ac.jp