Virus infection induces neuroinflammation by autoimmune T cells in the multiple sclerosis model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07455
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kindai University
• Principal Investigator: Tsunoda Ikuo 近畿大学, 医学部, 教授 (00261529)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多発性硬化症 / 動物モデル / タイラーウイルス感染症 / 中枢神経系 / 自己免疫 / 炎症 / T細胞 / 自己抗体

Outline of Final Research Achievements

Multiple sclerosis (MS) is an inflammatory disease in the nervous system. Although the precise cause of MS is unknown, virus infections have been associated with the incidence of MS. Since we do not know how virus infections induce inflammation in the nervous system, we aimed to determine virus-induced pathogenic factors by which the immune cells could be overactivated, leading to immune cell infiltration in the nervous system and damaging the nerve fibers. We found that viral RNA genomes themselves can activate autoimmune responses, causing inflammation in the nervous system. We also found that viral infections altered the gut microbiota (flora), activating/changing several subsets of antibody responses. To determine the roles of these multiple immune factors, we applied several bioinformatics methods to big data. We found that exploratory factor analysis is the most useful method to determine not only the pathogenic factors but also protective factors.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症（MS）の治療には症状の緩和を狙った複数の免疫修飾療法があるが、自己免疫素因をもった個人における MS の発症予防策は現在のところない。これは MS 研究がこれまで発症後の免疫動態の観察に主眼がおかれ、発症の機序に迫る研究が少なかったことによる。本研究により、MS 発症におけるウイルス自身あるいはウイルス感染症に由来する病気の増悪因子と疾患修飾因子が解明されたことで、これらを標的としたあらたな新しい MS 発症・増悪の予防法開発にも繋がることが期待される。また、因子の同定に有用であった探索型因子分析は、MSのみならず、他の疾患の原因・危険因子の究明などに応用可能なツールである。