Pathophysiological relevance of intracellular cholesterol metabolism in autoimmune diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16146
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Nagoya University
• Principal Investigator: Ito Ayaka 名古屋大学, 環境医学研究所, 助教 (80508333)
• Research Collaborator: Tontonoz Peter
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 自己免疫疾患 / 免疫細胞 / 脂質代謝 / 細胞内代謝 / 免疫代謝

Outline of Final Research Achievements

In this study, we analyzed genetic and drug-induced SLE model mice and elucidated that titers of autoantibodies and deposition of immunoglobulin in kidney were increased in the SLE model mice compared to the control mice. We also found that lipid content in immune cells was higher in SLE than control mice, and which was observed at the beginning of the development of SLE. On the other hand, there was no difference in serum lipid profile and hepatic gene expression of lipid metabolism between SLE and control mice. Administration of an agent to improve systemic lipid metabolism prevented the development of SLE. These findings suggest that lipid accumulation in immune cells is cell intrinsic effect and improvement of systemic lipid metabolism could be beneficial in the setting of autoimmune disease.

Free Research Field

細胞内代謝

Academic Significance and Societal Importance of the Research Achievements

本研究により、SLEの発症や進展過程において、早期から細胞自律的な脂質蓄積が起こることが明らかになり、近年注目されている免疫代謝領域における新たな発見となった。脂質代謝改善薬の投与がSLE発症を抑制したことより、今後は、全身とは独立して制御される免疫細胞内の脂質蓄積のメカニズムを解明し、免疫細胞内の脂質の量と質の変化に着目して、より詳細に研究を進める。SLEの病態メカニズムを明らかにするとともに、SLEの早期診断マーカーや食事療法の開発を目指したい。