Development of simulation method of neuro-immune regulation mechanism based on signal transduction pathway

• Project/Area Number: 16K00408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Okayama University of Science
• Principal Investigator: Yamada Satoshi 岡山理科大学, 工学部, 教授 (20393506)
• Project Period (FY): 2016-04-01 – 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 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ゲートウエイ反射 / シミュレーション / 炎症アンプ / IL-6 / NFkB / F759マウス / 血液脳関門 / ゲート形成 / コンピュータシミュレーション / 血管内皮細胞 / Th17 / Gateway Reflex / 免疫系・神経系相互作用 / シグナル伝達系

Outline of Final Research Achievements

The computer model which contains the neural system and immune system and simultaneously calculates intra-cellular reactions and the population of cell groups was developed by constructing a model of the gateway reflex. The model contained the inflammation amplifier of IL-6/STAT3 and noradrenaline/NFkB pathways in endothelial cells, and the movement of Th17 around the endothelial cells . The model mimicked the infiltration of Th17 across the blood-brain barrier. The model predicted the differences between F759 mice and the wild-type mice. The differences were consistent with the experimental results. The sensitivity analysis of the model suggested that IL-6/STAT3 pathway is more important than noradrenaline/NFkB pathway.

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症の発症モデルとなりうるコンピュータモデルを構築できたので、このモデルを用いて多発性硬化症の発症メカニズムの解析が可能になり、生物学実験を減らすことができる。また、新規薬物や新規治療法の候補をモデルを使って提案することが可能になる。また、このモデルは炎症一般のモデルにも拡張可能であるので、種々の疾患の原因となる慢性炎症のモデル構築につなげることができる。慢性炎症がモデル化できれば、多くの疾患の発症メカニズムをモデルを使って分析できるようになる。

Research Products

• [Presentation] Computer model of a gateway of immune cells across blood-brain barrier (2019)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Daisuke Kamimura, Masaaki Murakami
  • Organizer: Cytokines 2019
  • Int'l Joint Research
• [Presentation] Computer model of a gateway of immune cells across blood-brain barrier (2019)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Daisuke Kamimura, Masaaki Murakami
  • Organizer: 第４８回日本免疫学会学術集会
• [Presentation] Computer model of a gateway of immune cells across blood-brain barrier (2018)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Daisuke Kamimura, Masaaki Murakami
  • Organizer: 第４７回日本免疫学会総会・学術集会
• [Presentation] Computer model of a gateway of immune cells across blood-brain barrier (2017)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Yasunobu Arima, Masaaki Murakami
  • Organizer: 生命科学系学会合同年次大会（第４０回日本分子生物学会）
• [Presentation] Computer model of a gateway of immune cells across blood-brain barrier (2017)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Yasunobu Arima, Masaaki Murakami
  • Organizer: 第４６回日本免疫学会総会・学術集会
• [Presentation] Computer model of a gateway of immune cells across blood-brain barrier (2016)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Yasunobu Arima, Masaaki Murakami
  • Organizer: 第４５回日本免疫学会学術集会
  • Place of Presentation: 宜野湾
  • Year and Date: 2016-12-05
• [Presentation] 血液脳関門に存在する免疫細胞の侵入口形成のコンピュータモデル (2016)
  • Author(s): 山田訓、吉村昭彦、有馬康伸、村上正晃
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] Computer model analysis of the difference between F759 and wild type mice in rheumatoid-like arthritis emergence (2016)
  • Author(s): Satoshi Yamada, Akihiko Yoshimura, Toru Atsumi, Masaaki Murakami
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: オーストラリア メルボルン
  • Year and Date: 2016-08-21
  • Int'l Joint Research