Development of novel therapeutic agent for inflammatory bowel disease targeting the regulation of CD4 T cell metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16957
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Okayama University
• Principal Investigator: Takahara Masahiro 岡山大学, 大学病院, 助教 (80738427)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 炎症性腸疾患 / 腸管粘膜CD4T+細胞 / エネルギー代謝

Outline of Final Research Achievements

Metformin, a diabetes drug, has been reported to be involved in the immune response of T cells and other immune cells via activation of AMPK, a regulator of energy, and has attracted attention as a possible mechanism of action. In the present study, the anti-inflammatory action of Metformin on CD4+ T cells of the colitis mucosa and its mechanism were examined using a mouse model of chronic colitis, focusing on AMPK activation.
Metformin suppressed the intestinal inflammation in a mouse model of chronic intestinal inflammation. One of the mechanism was suggested to be via activation of AMPK by suppressing mitochondrial oxidative phosphorylation and adenosine triphosphate production.

Free Research Field

炎症性腸疾患

Academic Significance and Societal Importance of the Research Achievements

本研究はCD4+ T細胞特異的大腸炎を誘発する炎症性腸疾患(IBD)モデルマウスを用いて、メトホルミンによる腸管粘膜CD4+T細胞のAMPK活性化が、腸炎の改善につながることを新たに示した。本研究は、腸管粘膜のCD4+T細胞のエネルギー代謝の抑制機序についての新たな知見を提供するものであり、IBDの治療法の開発に安全で有用な新しい治療標的を導く可能性があること、また、メトホルミンをはじめとしたエネルギー代謝を改善する薬剤は、IBDの新しい治療薬として可能性があることを示唆する結果であった。