| セッション情報 |
The 2nd JSGE International Topic Conference Poster Session
Cytokine
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| タイトル |
IT-P-21：Progressive Depletion of Hepatic NKT Cells in Steatohepatitis with Tumorigenesis Caused by Hepatocyte-specific Pten Deficiency
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| 演者 |
Miyaji Takashi（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan） |
| 共同演者 |
Ikejima Kenichi（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan）, Hosoya Satoko（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan）, Arai Kumiko（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan）, Aoyama Tomonori（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan）, Kon Kazuyoshi（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan）, Yamashina Shunhei（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan）, Watanabe Sumio（Department of Gastroenterology, Juntendo University Graduate School of Medicine, Japan） |
| 抄録 |
Background：The innate immune system plays a pivotal role in the pathogenesis of NASH；however, the role of hepatic NKT cells in tumorigenesis based on steatohepatitis has not been well elucidated. Here, we investigated the changes in NKT cells in hepatocyte-specific Pten（Phosphatase and Tensin Homolog Deleted from Chromosome 10）knockout mice, which spontaneously develop steatohepatitis with tumorigenesis. Methods：Hepatocyte-specific Pten-KO（AlbCrePtenflox/flox）and wild type（WT；C57Bl/6）mice fed normal diet for up to 50 weeks were used. NKT（CD3+NK1.1+）, NK（CD3-NK1.1+）, and Gr1+CD11b+cells in hepatic mononuclear cells（MNCs）were analyzed by flow cytometry. Hepatic mRNA levels for IL-4, IL-13, IL-10, IFNγ, TNFα, TGFβ, and CCL2 were detected by real-time RT-PCR. Results：In Pten-KO mice, percentages of NKT cells in hepatic MNCs were progressively decreased, and hepatic mRNA levels of IL-4, IL-13, and IL-10 were significantly decreased from the early phase. Remarkable increases in Gr1+CD11b+myeloid suppressor cells, which inactivate NKT cells, were observed in 30 week-old Pten-KO, in which overt tumor was not detectable. At the same phase, hepatic mRNA levels of TNFα, CCL2, and TGFβ were also elevated significantly. Conclusion：These findings support the hypothesis that myeloid suppressor cells are involved in the depletion of hepatic NKT cells, leading to Th1-favored microenvironment, thereby blunting tumor surveillance in steatohepatitis. |
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