Age-related changes in innate immune regulation by NKT / NK cells and exacerbation mechanism in fatty liver disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17063
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Juntendo University
• Principal Investigator: Nakadera Eisuke 順天堂大学, 医学部, 助教 (20596225)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: NKT細胞 / 老年学 / 非アルコール性脂肪肝炎 / 非アルコール性脂肪性肝疾患

Outline of Final Research Achievements

To elucidate the exacerbation mechanism of steatohepatitis with aging, we developed steatohepatitis animal models induced by high-fat, high-cholesterol diet (HFHC) using aged type I NKT cell knockout mice and type I/II NKT cell knockout mice. As a result, it was revealed that type I NKT cells play a major role in the age-related upregulation of inflammatory cytokines and liver fibrosis after HFHC. In addition, it was shown that Type II NKT cells mainly contribute to the upregulation of some chemokines and have some effect on mild steatohepatitis in young mice, but their impact on development of steatohepatitis are relatively decreased in aged mice.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪肝炎（NASH)の病態解明は急務であり、本研究の結果は加齢によるNASHの増悪プロセスにおけるNKT細胞の役割を解明した、学術的に重要なものである。今後type I NKT細胞の活動性を指標としたNASHの高リスク群の囲い込み、NASHの病態進展リスク評価、type I NKT細胞を標的としたNASHの新規治療法の確立につながることが期待できる。世界的に罹患数が増加し、肝硬変、肝がんの背景因子として重要なNASHの診断、治療法の確立に貢献しうる、将来の医療に貢献しうる意義の大きな結果が得られた。