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Does the role of Th17/Treg cells differ depending on the disease stage?

Research Project

Project/Area Number 16H07356
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionKindai University

Principal Investigator

TSUNODA Ikuo  近畿大学, 医学部, 教授 (00261529)

Research Collaborator OMURA Seiichi  近畿大学, 医学部, 助教 (80462480)
Project Period (FY) 2016-08-26 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsウイルス / 多発性硬化症 / 免疫学 / 自己免疫 / 動物モデル / 神経ウイルス学 / Tリンパ球 / トランスレーショナルリサーチ / マイクロアレイ / 次世代シーケンシング / ウィルス
Outline of Final Research Achievements

In mulitple sclerosis (MS), it has been proposed that IL-17-producing T helper (Th)17 cells are detrimental, and regulatory T cells (Tregs) are protective. Using a viral model for MS, Theiler's murine encephalomyelitits virus (TMEV)-induced demyelinating disease (TMEV-IDD), we aimed to clarify the roles of Th17 cells and Tregs. Using methods to increase the numbers of Th17 cells or Tregs ("gain-of-function" approach), we found that Th17 cells have three roles: 1) exacerbation of inflammation, 2) suppression of anti-viral immunity, and 3) neuroprotection and that Tregs have two roles: 1) suppression of inflammation and 2) suppression of anti-viral immunity. Therefore, Th17 cells and Tregs may play either beneficial or detrimental roles in MS, depending on the causes or disease course. These findings can be used for future tailor-made treatment of MS, in which Th17 cells and Tregs should be modulated depending on the conditions of patients with MS.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • Research Products

    (34 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results) Book (2 results) Remarks (8 results)

  • [Int'l Joint Research] LSU Health Sciences Center/Louisiana State University-Shreveport(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ルイジアナ州立大学医学部/ハワイ大学 University of Hawaii at Manoa/Louisiana State University-Shreveport(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] T-bet, but not Gata3, overexpression is detrimental in a neurotropic viral infection2017

    • Author(s)
      Sato Fumitaka、Kawai Eiichiro、Martinez Nicholas E.、Omura Seiichi、Park Ah-Mee、Takahashi Satoru、Yoh Keigyou、Tsunoda Ikuo
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 10496-10496

    • DOI

      10.1038/s41598-017-10980-0

    • NAID

      120007134862

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CCL28-deficient mice have reduced IgA antibody-secreting cells and an altered microbiota in the colon2017

    • Author(s)
      Matsuo Kazuhiko、Nagakubo Daisuke、Yamamoto Shinya、Shigeta Akiko、Tomida Shuta、Fujita Mitsugu、Hirata Takako、Tsunoda Ikuo、Nakayama Takashi、Yoshie Osamu
    • Journal Title

      The Journal of Immunology

      Volume: 200 Issue: 2 Pages: 800-809

    • DOI

      10.4049/jimmunol.1700037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphatic system and gut microbiota affect immunopathology of neuroinflammatory diseases, including multiple sclerosis, neuromyelitis optica and Alzheimer's disease2017

    • Author(s)
      Tsunoda Ikuo
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 8 Issue: 3 Pages: 177-179

    • DOI

      10.1111/cen3.12405

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studies2017

    • Author(s)
      Park Ah-Mee、Omura Seiichi、Fujita Mitsugu、Sato Fumitaka、Tsunoda Ikuo
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 8 Issue: 3 Pages: 215-232

    • DOI

      10.1111/cen3.12401

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influx and Efflux of Immune Cells in the Central Nervous System2017

    • Author(s)
      M Fujita、S Omura、F Sato、AM Park、I Tsunoda
    • Journal Title

      Anatomy & Physiology: Current Research

      Volume: 07 Issue: 04 Pages: 4-5

    • DOI

      10.4172/2161-0940.1000274

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three immune-mediated disease models induced by Theiler’s virus: multiple sclerosis, seizures, and myocarditis.2016

    • Author(s)
      Tsunoda I, Sato F, Omura S, Fujita M, Sakiyama N, and Park AM.
    • Journal Title

      Clin Exp Neuroimmunol

      Volume: 7 Issue: 4 Pages: 330-345

    • DOI

      10.1111/cen3.12341

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neuropathogenesis of Zika virus infection: Potential roles of antibody-mediated pathogy2016

    • Author(s)
      Tsunoda I, Omura S, Kusunoki S, Sato F, Fujita M, Park A-M, Hasaonvic F, Yanagihara R, Nagata S.
    • Journal Title

      Acta Medica Kindai Univ

      Volume: 41 Pages: 37-52

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Computational analysis determined the homogeneities and heterogeneieties between two distinct EAE models for progressive multiple sclerosis2017

    • Author(s)
      Omura S, Sato F, Martinez NE, Park A-M, Fujita M, Kilgore PCSR, Cvek, U, Trutschl M, Minagar A, Alexander JS, and, Tsunoda I
    • Organizer
      7th Sendai Conference 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] An RNA virus triggers inflammatory demyelination in the central nervous system by activating anti-myelin autoimmune T cells.2017

    • Author(s)
      Sato F, Legaux KN, Creason TG, Omura S, Park A-M, Fujita M, Stokes KY and Tsunoda I
    • Organizer
      7th Sendai Conference 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Factor Analysis Associated Anti-Glycolipid Antibodies with Clinical Data in Guillain-Barré Syndrome2017

    • Author(s)
      Omura S, Shimizu K, Morikawa M, Kuwahara M, Kawamura T, Mori T, Kusunoki S, and Tsunoda I
    • Organizer
      Informatics in Biology, Medicine and Pharmacology (IIBMP2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Viral infection activates myelin-specific T cells, triggering MS-like CNS inflammatory demyelination2017

    • Author(s)
      Sato F, Omura S, Park A-M, Fujita M, Stokes KY, and Tsunoda I
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bioinformatics analysis determined the CNS and peripheral lymphoid surrogate biomarker candidates between two distinct EAE models for progressive multiple sclerosis2017

    • Author(s)
      Omura S, Sato F, Martinez NE, Park A-M, Cvek U, Minagar A, Alexander JS, and Tsunoda I
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bioinformatics analyses identified phase-specific heart biomarkers and blood surrogate markers for a mouse model of viral myocarditis2017

    • Author(s)
      Omura S, Sato F, Park A-M, Fujita M, Alexander JS, Kilgore CSR, Cvek U, and Tsunoda I
    • Organizer
      The 65th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多発性硬化症の遺伝子プロファイル主成分分析PCAによるリンパ管バイオマーカーの同定2017

    • Author(s)
      角田郁生、尾村誠一、佐藤文孝、朴雅美、藤田貢
    • Organizer
      第90回日本産業衛生学会 アレルギー・免疫毒性研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] タイラーウイルス誘導性脳脊髄炎モデルにおける制御性T細胞の役割2017

    • Author(s)
      佐藤文孝、Nicolas Martinez, Fridrik Karlsson, 尾村誠一、朴雅美、藤田貢, Matthew Grishma, 角田郁生
    • Organizer
      第27回日本サイトメトリー学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Rを用いた主成分分析による多発性硬化症マウスモデル病態・病理像関連バイオマーカーの同定2017

    • Author(s)
      尾村誠一、佐藤文孝、Nicholas E. Martinez、朴雅美、藤田貢、Phillip C.S.R. Kilgore、Urska Cvek、Marjan Trutschl、Alireza Minagar、J. Steven Alexander、角田郁生
    • Organizer
      第76回近畿大学医学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ウイルスによる自然発症自己免疫モデルの増悪2017

    • Author(s)
      佐藤文孝、尾村誠一、朴雅美、藤田貢、角田郁
    • Organizer
      第76回近畿大学医学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 転写因子T-bet過剰発現は神経向性ウイルス感染を増悪させる2017

    • Author(s)
      佐藤文孝、川合英一郎、ニコラス・マルチネス、尾村誠一、藤田貢、朴雅美、崎山奈美江、高橋智、楊景堯、角田郁生
    • Organizer
      第29回日本神経免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 次世代シークエンシングを用いたウイルス性脳脊髄炎モデルの解析; リンパ管分子発現低下が免疫細胞の中枢神経内停滞に関連する2017

    • Author(s)
      尾村誠一、佐藤文孝、藤田貢、朴雅美、J. Steven Alexander、Phillip C.S.R. Kilgore、Urska Cvek、角田郁生
    • Organizer
      第22回日本神経感染症学会総会・学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 免疫病理学、バイオインフォマティクスによる多発性硬化症動物モデルの研究2017

    • Author(s)
      角田郁生
    • Organizer
      第47回神戸ラボ全体研究会議
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ウイルス感染によって誘発される炎症性脱髄と軸索変性のメカニズム。2016

    • Author(s)
      角田郁生、佐藤文孝、尾村誠一、崎山奈美江、朴雅美、藤田貢.
    • Organizer
      第21回日本神経感染症学会総会・学術大会
    • Place of Presentation
      金沢東急ホテル (石川県)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 進行型多発性硬化症モデルでは血管接着分子の発現増加、BBB/リンパ管分子の発現減少が病因に相関する2016

    • Author(s)
      尾村誠一、佐藤文孝、J. Steven Alexander, Phillip C.S.R. Kilgore, Urska Cvek, Marjan Trutschl、角田郁生
    • Organizer
      第28回日本神経免役学会学術集会
    • Place of Presentation
      長崎ブリックホール (長崎県)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
  • [Book] MSの動物モデルについて教えてください 吉良潤一編集 <シリーズ>神経内科 Clinical Questions & Pearls「中枢性脱髄疾患」2018

    • Author(s)
      角田郁生
    • Publisher
      中外医学社
    • Related Report
      2017 Annual Research Report
  • [Book] Role of CD4+ T lymphocytes in pathophysiology of multiple sclerosis. In: Multiple Sclerosis: A Mechanistic View. Minagar A (Ed)2016

    • Author(s)
      Sato F, Omura S, Jaffe SL and Tsunoda I.
    • Total Pages
      28
    • Publisher
      Elsevier, London, UK
    • Related Report
      2016 Annual Research Report
  • [Remarks] 47th Kobe Laboratory General Research Congress

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-271.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] Miyazaki Multiple Sclerosis Seminar

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-263.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 2017 Japanese Society for Virology

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-262.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] Japanese Society for Neuroinfectious Diseases

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-261.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] Japanese Society of Neuroimmunology Meeting

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-260.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 2016 Japan Society for Neuroimmunology Meeting

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-220.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] Japanese Society for Neuroinfectious Diseases

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-224.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] Dr. Yanagihara Kindai Microbiology seminar

    • URL

      http://tsunodalaboratory.blog.fc2.com/blog-entry-221.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-09-02   Modified: 2022-05-23  

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