2021/10/11
Keio University School of Medicine
Japan Agency for Medical Research and Development
An international joint research team, including Associate Professor Hayato Takahashi and Professor Masayuki Amagai from the Department of Dermatology, Keio University School of Medicine, and Dr. Yuka Kanno (Staff Scientist) and Dr. John O'Shea (Scientific Director) from the U.S. National Institutes of Health, has discovered a new inflammation-suppressing mechanism related to cholesterol metabolism.
Previous studies on the immune and metabolic systems have been conducted separately, and their respective roles have been understood independently. This study has revealed a mechanism by which the immune system utilizes lipid metabolism to resolve inflammation. The findings of this basic research are expected to lead to the development of new treatments for diseases involving inflammation.
In all cells, including immune cells, cholesterol, a type of lipid, is an essential substance for cellular activity. When intracellular cholesterol is deficient, a mechanism is activated to stimulate cholesterol synthesis and maintain appropriate concentration levels. Substances that play a crucial role in this mechanism include cholesterol and oxysterols, which are formed by the oxidation of cholesterol. It is believed that the same mechanism exists in immune cells.
The research team has now found that CD4-positive T cells, a type of immune cell, secrete 25-hydroxycholesterol (25-OHC). 25-OHC is a type of oxysterol. The secreted 25-OHC acts on surrounding immune cells, weakening their cholesterol synthesis function through the cholesterol concentration-regulating mechanism, thereby causing a state of cholesterol depletion. As a result, the team clarified that inflammatory immune cells are unable to secure the cholesterol necessary for their activity and undergo cell death, leading to the resolution of inflammation.
The results of this research were published in the online edition of the international academic journal "Science Immunology" on October 8, 2021 (U.S. Eastern Standard Time).
Please see below for the full press release.