Development of immune therapy for non-alcoholic fatty liver disease with iNKT cells
| Project/Area Number |
16K09376
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上田 しのぶ 東京医科大学, 医学部, 助手 (00521874)
須藤 カツ子 東京医科大学, 医学部, 兼任講師 (50126091)
村上 善基 大阪市立大学, 大学院医学研究科, 准教授 (00397556)
梅澤 明弘 国立研究開発法人国立成育医療研究センター, 再生医療センター, 副所長/再生医療センター長 (70213486)
黒田 雅彦 東京医科大学, 医学部, 主任教授 (80251304)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | NASH / 肝臓 / 非アルコール性脂肪性肝炎 / iNKT細胞 / 脂肪性肝炎 |
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| Outline of Final Research Achievements |
The patients with Non-alcoholic steatohepatitis (NASH) increase in recent years. NASH progresses to be cirrhosis and hepatocellular carcinoma at a high rate. Because there is no effective treatment yet, development of therapy for NASH is desired. We tried to apply immunotherapy to the treatment of NSAH. We focused on fat-targeted iNKT cells and tried to make model mice to confirm the distribution of iNKT cells in NASH-liver. Model mice were used in high-week-aged mice and mice in which glucose metabolism abnormalities were induced by suppressing the secretion of insulin by the administration of streptozotocin (STZ). Degenerative lives were obtained in STZ and high-fat diet treatment mice. iNKT cells in the liver on NASH were decreased compared with that in non-treatment mice.
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| Academic Significance and Societal Importance of the Research Achievements |
NASHは進行すると肝硬変、肝細胞がんを発症する増加傾向にある疾患で、効的な治療法が未だ開発されていない。治療法の開発に必要なモデル動物の作成を試みた。マウスの作成には高脂肪飼料を給餌したのみの群ではNASH用の組織像は認められなかったインスリンの分泌を抑制することで糖代謝異常を誘導させたマウスに、高脂肪食を給餌すると脂肪による肝臓組織の変性が認められた。血清生化学測定でも肝臓の機能障害が認められた。この組織中のiNKT細胞の存在は未処置群に対して減少した。この結果からiNKT細胞を導入することでNASHによる病変の改善が予想される。現在、自己細胞からiNKT細胞の誘導法を検討している。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Development of novel small hairpin RNAs that do not require processing by dicer or AGO22016
Author(s)
Ohno S, Itano K, Harada Y, Asada K, Oikawa K, Kashiwazako M, Okuyama H, Kumagai K, Takanashi M, Sudo K, Ikeda N, Kuroda M.
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Journal Title
Mol Ther
Volume: 24
Issue: 7
Pages: 1278-1289
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Development of novel Dicer- and Ago2-independent small hairpin RNAs.2016
Author(s)
Ohno S, Itano K, Harada Y, Asada K, Oikawa K, Kashiwazako M, Okuyama H, Kumagai K, Takanashi M, Sudo K, Ikeda N, Kuroda M.
Organizer
American Society of Gene & Cell Therapy(ASGCT) 19th Annual Meeting. (第19回米国遺伝子治療学会)
Place of Presentation
Washington,DC, USA.
Year and Date
2016-05-04
Related Report
Int'l Joint Research
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