Regulation of virus-induced encephalomyelitis by immunoglobulin-like receptors

• Project/Area Number: 16K09703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: NAKAMURA Akira 東北医科薬科大学, 医学部, 教授 (20344723)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 神経科学 / 多発生硬化症 / 多発性硬化症 / 免疫学

Outline of Final Research Achievements

Theiler's murine encephalomyelitis virus (TMEV) is a representative disease model of multiple sclerosis (MS) Although we have showed that TMEV binds to the immunoglobulin like receptor, Siglec-E, the expression of Siglec-E alone was founded to be insufficient for viral infection in non-TEMV infected strain. On the other hand, because TMEV does not bind to plasmacytoid dendritic cells (pDCs), we investigated the membrane lipid components in pDCs and DC, and found that the ganglioside GM1 was less in pDCs. Moreover, cholera toxin B subunit and TMEV capsid protein VP1 were co-localized in DCs, suggesting that GM1 act as the entry receptor of TMEV infection.

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症（MS）は、中枢神経系の慢性脱髄性疾患で、ミエリン塩基性蛋白など自己抗原に対する自己免疫反応によって生じる代表的なヒト自己免疫疾患である。再発と緩解を繰り返すことから、原因の一つにウイルス感染があることが指摘されている。代表的な疾患モデルとして、タイラーマウス脳脊髄炎ウイルス (TMEV) 感染による脱随疾患が知られているが、細胞表面に結合する受容体は不明なままであった。本研究では、TEMVが細胞膜上に発現するガングリオシドに結合することを見出した。ガングリオシドがMSのみならずウイルス感染防御の新たな治療標的となることを示唆した結果であり、極めて意義のある知見と考えられた。

Research Products

• [Journal Article] Identification of Secretory Leukoprotease Inhibitor As an Endogenous Negative Regulator in Allergic Effector Cells (2017)
  • Author(s): Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Toshiyuki Takai, Toshiaki Kikuchi, Toshihiro Nukiwa, Akira Nakamura
  • Journal Title: Frontiers in Immunology Volume: 8 Pages: 1538-1538
  • DOI: 10.3389/fimmu.2017.01538
  • Peer Reviewed / Open Access
• [Journal Article] Polymorphisms of immunoglobulin receptors and the effects on clinical outcome in cancer immunotherapy and other immune diseases: a general review (2017)
  • Author(s): Tomonori Kaifu,Akira Nakamura
  • Journal Title: International Immunology Volume: 29 Issue: 7 Pages: 319-325
  • DOI: 10.1093/intimm/dxx041
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of immune and neural function via leukocyte Ig-like receptors (2017)
  • Author(s): Kazuya Takada, Akira Nakamura
  • Journal Title: Journal of Biochemistry Volume: 162 Issue: 2 Pages: 73-80
  • DOI: 10.1093/jb/mvx036
  • Peer Reviewed / Open Access
• [Journal Article] TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin. (2016)
  • Author(s): Yabe-Wada T, Matsuba S, Takeda K, Sato T, Suyama M, Ohkawa Y, Takai T, Shi H, Philpott CC, Nakamura A.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 26566-26566
  • DOI: 10.1038/srep26566
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A critical role of Dectin-1 in hypersensitivity pneumonitis (2015)
  • Author(s): Higashino-Kameda M, Yabe-Wada T, Matsuba S, Takeda K, Anzawa K, Mochizuki T, Makimura K, Saijo S, Iwakura Y, Toga H, Nakamura A
  • Journal Title: Inflamm Res Volume: 65 Issue: 3 Pages: 235-44
  • DOI: 10.1007/s00011-015-0910-1
  • Peer Reviewed / Open Access
• [Presentation] The search for Theiler's murine encephalomyelitis virus receptor. (2018)
  • Author(s): Kazuya Takeda, Tomonori Kaifu, Akira Nakamura
  • Organizer: Annual Meeting of The Japanease Society for Immunology
• [Presentation] タイラーマウス脳脊髄炎ウイルス受容体の探索 (2018)
  • Author(s): 武田和也、姫田敏樹、海部知則、大原義朗、中村晃
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] SLPI negatively regulates LPS-induced eosinophil activation via inhibition of Elk-1 phosphorylation (2017)
  • Author(s): Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Nobuyuki Onai, Toshiyuki Takai, Akira Nakamura
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Theiler’s virus fails to stimulate plasmacytoid dendritic cell (2017)
  • Author(s): Kazuya Takeda, Shintaro Matsuba, Toshiki Yabe-Wada, Akira Nakamura
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] タイラーマウス脳脊髄炎ウイルス感染における形質細胞様樹状細胞の役割 (2017)
  • Author(s): 武田和也、姫田敏樹、大原義朗、中村晃
  • Organizer: 第29回日本神経免疫学会学術集会
• [Presentation] TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin (2016)
  • Author(s): Toshiki Yabe-Wada, Shintaro Matsuba, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Yasuyuki Ohkawa, Toshiyuki Takai, Haifeng Shi, Caroline C. Philpott, Akira Nakamura
  • Organizer: Gordon Research Conference on Protein Processing, Trafficking and Secretion
  • Place of Presentation: Colby-Sawyer College, New London, NH, USA
  • Int'l Joint Research / Invited
• [Presentation] タイラーマウス脳脊髄炎ウイルス感染は形質細胞様樹状を刺激しない (2016)
  • Author(s): 武田和也、姫田敏樹、大原義朗、中村晃
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌コンベンションセンター、札幌市、北海道
• [Presentation] 好塩基球・好酸球におけるSLPIの制御機構の解明 (2016)
  • Author(s): 松葉慎太郎、和田俊樹、武田和也、佐藤哲也、須山 幹太、高井俊行、中村晃
  • Organizer: 第65回日本アレルギー学会
  • Place of Presentation: 東京国際フォーラム、千代田区、東京都
• [Remarks] アレルギー反応を恒常的に制御するタンパク質の発見
  • URL: http://www.tohoku-mpu.ac.jp/medicine/news-medicine/8814/