Possible pathomechanism of multiple sclerosis from the perspective of abnormal mucosal immune responses

• Project/Area Number: 20590991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: KAWACHI Izumi Niigata University, 医歯学総合病院, 助教 (40432083)
• Co-Investigator(Kenkyū-buntansha): TOYOSHIMA Yasuko 新潟大学, 脳研究所, 助教 (20334675)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 中枢神経系脱髄疾患 / 多発性硬化症 / 視神経脊髄炎 / 粘膜免疫 / innate T細胞 / interleukin-17 / 衛生仮説 / innata T細胞 / 中枢神経系脱髄性疾患 / 脱髄性疾患

Research Abstract

The prevalence of multiple sclerosis (MS) and Crohn's disease have increased since 1960s in Japan. The 'hygiene hypothesis' has been proposed for immunopathogenesis of MS. The distinct population of double negative T cells (DNT) expressing IL-17 was identified in patients with MS. As most of DNT cells are composed of innate T cells including γδT cells and IL-17-expressing cells are most abundant at steady state in gut-associated tissues, we suspect that the production of IL-17 derived from mucosal associated cells including not only T_H-17 per se but also innate T cells might be critical elements contributing to MS.

Research Products

• [Journal Article] No relapse of neuromyelitis optica during drug-induced B-lymophopenia with hypogammaglobulinemia. (2010)
  • Author(s): 河内泉
  • Journal Title: Neurology 75 Pages: 1745-1747
  • Peer Reviewed
• [Journal Article] Treatment-responsive opsoclonus-ataxia associated with ovarian teratoma. (2010)
  • Author(s): Kawachi I, Saji E, Toyoshima Y, Dalmau J, Nishizawa M
  • Journal Title: J Neurol Neurosurg Psychiatry 81 Pages: 581-582
  • Peer Reviewed
• [Journal Article] Potential role of cellular immunity in neuromyleitis optica. (2010)
  • Author(s): 河内泉
  • Journal Title: J Neuroimmunol 228 Pages: 138-138
• [Journal Article] Diagnosis and management of paraneoplastic neurological syndromes. (2010)
  • Author(s): 河内泉
  • Journal Title: Brain Nerve 62 Pages: 319-330
  • NAID: 40017067152
• [Journal Article] Humoral and cellular immune responses in neuromyelitis optica. (2010)
  • Author(s): 河内泉
  • Journal Title: Rinsho Shinkeigaku 50 Pages: 873-874
  • NAID: 130004504669
• [Journal Article] 膠原病に伴う神経・筋障害:診断と治療の進歩.肥厚性硬膜炎 (2010)
  • Author(s): 河内泉, 西澤正豊
  • Journal Title: 日本内科学会雑誌 99 Pages: 1821-1829
• [Journal Article] Involvement of Onuf's nucleus in Machado-Joseph disease : a morphometric and immunohistochemical study. (2010)
  • Author(s): Toyoshima Y
  • Journal Title: Acta neuropathol 120 Pages: 439-448
  • Peer Reviewed
• [Journal Article] Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease : a distinct clinicopathological and biochemical disease entity. (2010)
  • Author(s): Toyoshima Y
  • Journal Title: Acta Neuropathol 120 Pages: 21-32
  • Peer Reviewed
• [Journal Article] Treatment responsive opsoclonus-ataxia associated with ovarian teratoma. (2010)
  • Author(s): Kawachi I, Saji E, Toyoshima Y, Dalmau J, Nishizawa M.
  • Journal Title: JNeurol Neurosurg Psychiatry Volume: 81 Pages: 581-582
  • Peer Reviewed
• [Journal Article] No relapse of neuromyelitis optica during drug induced B-lymphopeniawith hypogammaglobulinemia. (2010)
  • Author(s): Tanaka Y, Kimura K, Kawachi I, Inuzuka T.
  • Journal Title: Neurology Volume: 75 Pages: 1745-1747
  • Peer Reviewed
• [Journal Article] 特集:膠原病に伴う神経・筋障害:診断と治療の進歩.I.彦原病・類縁疾患に伴う神経・筋障害の診断と治療.肥厚性硬膜炎 (2010)
  • Author(s): 河内泉, 西澤正豊
  • Journal Title: 日本内科学会雑誌 Volume: 99 Pages: 1821-1829
• [Journal Article] Humoral and cellular immune responses in neuromyelitis optica. (2010)
  • Author(s): Kawachi I, et.al.
  • Journal Title: Rinsho Sinkeigaku Volume: 50 Pages: 873-874
  • NAID: 130004504669
• [Journal Article] Pahotlogical and immunological profiles of a limited form of neuromyelitis optica with myelitis. (2009)
  • Author(s): 河内泉
  • Journal Title: Neurology 73 Pages: 1628-1637
  • Peer Reviewed
• [Journal Article] T lymphocytes : Helpers. (2009)
  • Author(s): Kawachi I, Kondo T.
  • Journal Title: ENCYCLOPEDIA OF LIFE SCIENCE (ELS)
  • Peer Reviewed
• [Journal Article] Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology. (2009)
  • Author(s): 河内泉
  • Journal Title: Acta Neuropathol. 117 Pages: 45-53
  • Peer Reviewed
• [Journal Article] 多発性硬化症のゲノム解析 (2009)
  • Author(s): 西澤正豊, 河内泉
  • Journal Title: 医学のあゆみ 230 Pages: 616-619
• [Journal Article] Cerebellar involvement in progressive supranuclear palsy : a clinicopathological study. (2009)
  • Author(s): Toyoshima Y
  • Journal Title: Mov Disord 24 Pages: 1312-1318
  • Peer Reviewed
• [Journal Article] Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death. (2009)
  • Author(s): Toyoshima Y
  • Journal Title: Brain 132 Pages: 1810-1819
  • Peer Reviewed
• [Journal Article] Selective occurrence of TDP-43-immunoreactive inclusions in the lower motor neurons in Machado-Joseph disease. (2009)
  • Author(s): Toyoshima Y
  • Journal Title: Acta Neuropathol 118 Pages: 553-560
  • Peer Reviewed
• [Journal Article] Sporadic amyotrophic lateral sclerosis : widespread multisystem degeneration with TDP-43 pathology in a patient after long-term survival on a respirator. (2009)
  • Author(s): Toyoshima Y
  • Journal Title: Neuropathology 29 Pages: 689-696
  • NAID: 10028192795
  • Peer Reviewed
• [Journal Article] Patients with limbic encephalitis associated with anti-voltage-gated potassium channel antibodies who presented with insomnia and hand tremor. (2008)
  • Author(s): 河内泉
  • Journal Title: Rinsho Shinkeigaku 48 Pages: 338-342
  • NAID: 10021187638
  • Peer Reviewed
• [Journal Article] 傍腫瘍性神経症候群:診断と治療の進歩 (2008)
  • Author(s): 河内泉
  • Journal Title: 日本内科学会雑誌 97 Pages: 63-69
• [Journal Article] The distinct lineage : Double negative T cells expressing IL-17 in multiple sclerosis. (2008)
  • Author(s): 河内泉
  • Journal Title: J of Neuroimmunol 203 Pages: 163-163
• [Journal Article] Sporadic amyotrophic lateral sclerosis : two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. (2008)
  • Author(s): Toyoshima Y
  • Journal Title: Acta Neuropathol 116 Pages: 169-182
  • Peer Reviewed
• [Journal Article] 傍腫瘍性神経症候群 : 診断と治療の進歩. 特異的診断法・治療法. 診断のアプローチ. (2008)
  • Author(s): 河内泉
  • Journal Title: 日本内科学会雑誌 97巻 Pages: 63-69
• [Presentation] Potential role of cellular immunity in neuromyelitis optica. (2011)
  • Author(s): 河内泉
  • Organizer: Keystone symposia "Genetics, Immunology and Repair in Multiple Sclerosis".
  • Place of Presentation: Taos, USA.
• [Presentation] Potential role of cellular immunity in neuromyleitis optica. (2010)
  • Author(s): Kawachi I
  • Organizer: The 10th International Congress of Neuroimmunology
  • Place of Presentation: Sitges(Barcelona), Spain
  • Year and Date: 2010-10-26
• [Presentation] Potential role of cellular immunity in neuromyelitis optics. (2010)
  • Author(s): Kawachi I
  • Organizer: Keystone symposia"Genetics, Immunology and Repair in Multiple Sclerosis"
  • Place of Presentation: Taos, ITSA
  • Year and Date: 2010-08-22
• [Presentation] Humoral and cellular immunity in neuromyelitis optica. (2010)
  • Author(s): Kawachi I
  • Organizer: The 14th.International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-22
• [Presentation] Humoral and cellular immune responses in neuromyelitis optica. (2010)
  • Author(s): Kawachi I
  • Organizer: 第51回日本神経学会総会・シンポジウム
  • Place of Presentation: 東京, 日本
  • Year and Date: 2010-05-20
• [Presentation] Neuropsychiatric presentation of neuromyelitis optica spectrum disorders. (2010)
  • Author(s): Saji E, Toyoshima Y, Yanagawa K, Nishizawa M, Kawachi I
  • Organizer: The 62nd.Annual meeting of the American Academy of Neurology.
  • Place of Presentation: Tronto, Canada
  • Year and Date: 2010-04-10
• [Presentation] Potential role of cellular immunity in neuromyleitis optica. (2010)
  • Author(s): Kawachi I, Toyoshima Y, Yanagawa K, Saji E, Kakita A, Takahashi H, Nishizawa M
  • Organizer: The 10th International Congress of Neuroimmunology.
  • Place of Presentation: Sitges (Barcelona), Spain.
• [Presentation] Humoral and cellular immunity in neuromyelitis optica. (2010)
  • Author(s): Kawachi I, Yanagawa K, Saji E, Nishizawa M
  • Organizer: 第40回日本免疫学会, 14th.International Congress of Immunology合同学会
  • Place of Presentation: 神戸
• [Presentation] Humoral and cellular immune responses in neuromyelitis optica. (2010)
  • Author(s): 河内泉
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: シンポジウム招待講演
• [Presentation] Neuropsychiatric presentation of neuromyelitis optica spectrum disorders. (2010)
  • Author(s): Saji E, Toyoshima Y, Yanagawa K, Nishizawa M, Kawachi I
  • Organizer: The 62nd.Annual meeting of the American Academy of Neurology.
  • Place of Presentation: Tronto, Canada.
• [Presentation] 新規T細胞系列と多発性硬化症・NMO (2010)
  • Author(s): 河内泉,西澤正豊
  • Organizer: 第22回日本神経免疫学会学術集会
  • Place of Presentation: 招待講演
• [Presentation] 自然免疫機構からみた多発性硬化症 (2010)
  • Author(s): 河内泉
  • Organizer: 第1回関東MS研究会
  • Place of Presentation: 招待講演
• [Presentation] A potential plasticity of human IL-17-producing T cells and its reflection on pathogenicity of multiple sclerosis. (2009)
  • Author(s): 河内泉, 西澤正豊
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
• [Presentation] Pathological and immunological profiles of a limited form of neuromyelitis optica with myelitis. (2009)
  • Author(s): 河内泉
  • Organizer: International Symposium New aspects of Neuromyelitis optica (NMO).
  • Place of Presentation: Awaji, Japan
• [Presentation] Homogeneity of pathogenesis and heterogeneity of treatment response through long-term courses of neuromyelitis optica. (2009)
  • Author(s): Kawachi I, Yanagawa K, Nishizawa M
  • Organizer: The 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
  • Place of Presentation: Dusseldorf, German.
• [Presentation] Phenotypic features of T cells expressing RORγt in multiple sclerosis. (2009)
  • Author(s): 河内泉, 西澤正豊
  • Organizer: The 9th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS).
  • Place of Presentation: San Francisco, USA.
• [Presentation] The Distinct Lineage : Double Negative T Cells Expressing IL-17 in MS. (2009)
  • Author(s): 河内泉, 西澤正豊
  • Organizer: Keystone symposia "Multiple sclerosis".
  • Place of Presentation: Santa Fe, USA.
• [Presentation] Phenotype and functiona1 features of T cells expressing RORγt in multiple sclerosis (2008)
  • Author(s): Izumi Kawachi
  • Organizer: 第38回日本免疫学会学術集会
  • Place of Presentation: 京都, 日本
  • Year and Date: 2008-12-01
• [Presentation] The distinct lineage : double negative T cells expressing IL-17 in multiple sclerosis (2008)
  • Author(s): Izumi Kawachi
  • Organizer: 9^<th> Internationa1 Congress of Neuroimmunology (Workshop)
  • Place of Presentation: Fort Worth, Texas, USA
  • Year and Date: 2008-10-27
• [Presentation] Phenotypic and functional features of T cells expressing RORγt in multiple sclerosis. (2008)
  • Author(s): Kawachi I, Yanagawa K, Nishizawa M
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
• [Presentation] The distinct lineage : Double negative T cells expressing IL-17 in multiple sclerosis. (2008)
  • Author(s): Kawachi I, Musashi Arakawa, Kaori Yanagawa, Masatoyo Nishizawa
  • Organizer: The 9th International Congress of Neuroimmunology.
  • Place of Presentation: Fort Worth, USA.
• [Presentation] Identification of double negative T cells expressing IL-17 in multiple sclerosis. (2008)
  • Author(s): Kawachi I, Musashi Arakawa, Kaori Yanagawa, Masatoyo Nishizawa
  • Organizer: World Congress on Treatment and Research in Multiple Sclerosis (WCTRIMS).
  • Place of Presentation: Montreal, Canada
• [Remarks] ホームページ:新潟大学脳研究所神経内科.多発性硬化症基礎研究紹介
  • URL: http://www.bri.niigata-u.ac.jp/~neuroweb/laboratory/research_basic_005.html