2023 Fiscal Year Final Research Report
Role of liver X receptor on the regulation of hepatic immune cell population and function in nonalcoholic steatohepatitis
| Project/Area Number |
21K06862
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 49010:Pathological biochemistry-related
|
|---|
| Research Institution | Nihon University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | LXR / 核内受容体 / 肝臓 / Kupffer細胞 / マクロファージ / 肝炎 |
|---|
| Outline of Final Research Achievements |
The nuclear receptor liver X receptor (LXR) regulates cholesterol homeostasis and inflammatory response in macrophages. Due to the higher expression in liver, we focused on the effect of LXR deficiency on hepatic immune cell population and function using its knockout mice, and analyzed a model of diet-induced nonalcoholic steatohepatitis. We found that LXR-deficient mice with western-type diet feeding strongly induced hepatic immune cell infiltration and inflammation compared to wild-type mice. Single cell analysis unexpectedly showed that LXR deficiency affects an activity of a type of lymphocytes in addition to increased number of monocytes and macrophages. These results demonstrated that LXR plays an important role in regulating the progression of nonalcoholic steatohepatitis by dynamically altering population and function of various types of hepatic immune cells.
|
| Free Research Field |
生化学
|
| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪肝炎の進展には様々な免疫細胞の相互作用が重要であるが、細胞の種類が多い上に病態の進展過程や周辺環境により変化するためその制御は複雑であり、不明な点が多い。本研究において、シングルセル解析等の最先端の網羅的解析技術を用いて肝臓免疫細胞の分布や機能を詳細に解析した結果、LXRは、我々が先行研究で報告したKupffer細胞及びマクロファージ以外の細胞群の機能にも影響し、結果として肝炎進展時の肝臓免疫系全体を制御することを明らかにした。また現在、非アルコール性脂肪肝炎の有効な治療薬は存在しないことから、LXRリガンドが免疫細胞を標的としたNASHの治療薬となりうる可能性が示された。
|
