Immune System Found to Regulate Cholesterol to Resolve InflammationーResearch opens new doors for treating inflammatory diseasesー
November 16, 2021
Keio University School of Medicine
A research team at Keio University / National Institutes of Health has discovered a new anti-inflammatory mechanism related to cholesterol metabolism. The international joint research team was led by Dr. Hayato Takahashi and Dr. Masayuki Amagai (Department of Dermatology, Keio University School of Medicine, Japan) together with Dr. Yuka Kanno and Dr. John O'Shea (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, USA).
Until now, the immune and metabolic systems have been investigated independently, and their roles have been understood separately. Through this study, the research team has uncovered a mechanism by which the immune system uses lipid metabolism to constrain inflammation. The results of this basic research may lead to the development of new therapies for diseases associated with inflammation.
All cells, including immune cells, use cholesterol, a type of lipid, for cell activity. When cells lack cholesterol, they will actively synthesize it to maintain cholesterol concentration. Cholesterol, together with oxysterol, which is formed when cholesterol is oxidized, play important roles in this mechanism, and it is thought that the same mechanism exists within immune cells.
In this study, the team found that CD4+ T cells, a type of immune cell, secrete 25-hydroxycholesterol (25OHC), a type of oxysterol. The secreted 25OHC acts on surrounding immune cells, weakening their ability to synthesize cholesterol via a mechanism that regulates cholesterol concentrations in cells, resulting in cholesterol deprivation in the cells. Consequently, the inflammatory immune cells lack the cholesterol needed to maintain their activities, leading to cell death and resolution of the inflammation mediated by the immune cells.
The results of this research were published online in the international journal Science Immunology on October 8, 2021.
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