2022 Fiscal Year Final Research Report
Elucidation of the mechanism of NASH resolution via the gut-liver axis for future clinical application
| Project/Area Number |
20H04129
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 脂肪性肝炎 / 肝臓線維化 / 線維化修復 / 組織常在型CD8 T細胞 / 腸内細菌 |
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| Outline of Final Research Achievements |
In this study, we have identified an immunological mechanism by which the liver fibrosis pathology of nonalcoholic steatohepatitis (NASH) caused by long-term consumption of a high-fat, high-cholesterol diet is restored by dietary modification. Using an originally constructed mouse model, they found that "tissue-resident memory CD8T cells" are involved in the pathological recovery of NASH. The CD8T cells attract hepatic astrocytes, which are considered to be the main bad cells of fibrosis, via the CCR5/CCL5 axis, and induce apoptosis of activated astrocytes, thereby promoting recovery from fibrosis. These results are expected to lead to the development of new therapeutic and diagnostic strategies for NASH and other organ fibrosis diseases.
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| Free Research Field |
肝臓免疫
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| Academic Significance and Societal Importance of the Research Achievements |
今回申請者が見出したTrmは肝線維化修復において特異性、新規性が高く、将来的な治療標的候補として期待される。本研究課題の成果は、これまで明らかにされていない肝臓を中心とする臓器間ネットワークを介したTrmの誘導機序の解明という学問的意義のみならず、NASHの新たなバイオマーカーの確立と、今後の治療応用を見据えたProof of conceptの取得が期待される。さらに、線維化進展は肺線維症や腸管狭窄など肝臓以外の様々な臓器においても有効な治療法が存在せず、一刻も早い病態解明が待たれる領域であり、今後臓器特異性を含めて本研究成果を足がかりとして生体修復に関わる研究の発展と社会貢献が期待される。
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