Quality and amount of lipid in autoimmune diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K11765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Nagoya University
• Principal Investigator: Ito Ayaka 名古屋大学, 環境医学研究所, 講師 (80508333)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 自己免疫疾患 / 脂質代謝 / 免疫代謝

Outline of Final Research Achievements

Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. In this study, we found that dietary EPA supplementation ameliorated representative disease manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of autoimmune diseases.

Free Research Field

免疫代謝学

Academic Significance and Societal Importance of the Research Achievements

近年、細胞内の栄養代謝が免疫細胞機能を制御する「Immunometabolism - 免疫代謝」という学問領域が注目されている。本研究により、免疫細胞内の多価不飽和脂肪酸含有リン脂質を中心としたダイナミックな脂質の質的・量的変容がB細胞や樹状細胞などの免疫細胞機能に影響し、自己免疫応答を抑制するという、新しい免疫代謝のメカニズムが明らかとなった。また、EPAは魚油の成分であり、日常の食生活に取り入れられること、また、高脂血症治療薬としてすでに臨床応用されており、安全性が確認されていることから、EPAの摂取がSLEにおける新たな予防・治療法につながる可能性が示唆された。