Immune cell lipid reprogramming in chronic inflammatory diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 19KK0249
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Ito Ayaka 名古屋大学, 環境医学研究所, 講師 (80508333)
• Co-Investigator(Kenkyū-buntansha): 菅波 孝祥 名古屋大学, 環境医学研究所, 教授 (50343752) ; 原 雄一郎 公益財団法人東京都医学総合研究所, ゲノム医学研究センター, 主席研究員 (70709708)
• Project Period (FY): 2019-10-07 – 2024-03-31
• Keywords: 免疫代謝 / 脂質代謝 / 自己免疫

Outline of Final Research Achievements

Chronic inflammation is a common molecular basis underlying various chronic diseases, such as obesity, atherosclerosis and autoimmune diseases. We focused on lipid metabolism in immune cells to elucidate its significance in the regulation of immune cell functions and pathophysiology of chronic inflammatory diseases. We observed dynamic quantitative and qualitative alterations of lipids in immune cells of autoimmune diseases. In particular, the expression of enzymes that regulate fatty acid metabolism was found to be altered. We found that dietary eicosapentaenoic acid, a polyunsaturated fatty acid, ameliorated representative autoimmune lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. We also found that the endogenous intervention in lipid metabolism by deleting an enzyme regulating fatty acid metabolism resolved the disease pathology.

Free Research Field

免疫代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究により、自己免疫疾患の進展過程において、免疫細胞内の脂質変容が起こることが明らかとなった。特に、脂肪酸の内因的・外因的変化は、細胞膜のリン脂質組成を変容させることにより、免疫細胞の機能変容をもたらすこと、それによって自己免疫疾患病態も影響を受けることが新たに見出された。エイコサペンタエン酸は魚油の主成分であり、高脂血症薬としても臨床応用されていることから、自己免疫疾患の新たな治療標的となる可能性が示唆された。