Examination about the association between intrahepatic immunogenicity and the expression of regulatory molecules on hepatic T cells in mouse NASH model.
| Project/Area Number |
25461005
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
YAMAGUCHI KANJI 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50381950)
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| Co-Investigator(Renkei-kenkyūsha) |
ITOH YOSHITO 京都府立医科大学, 大学院医学研究科, 教授 (70244613)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 脂肪肝炎 / PD-1 / 脂肪肝 / 獲得免疫 / 免疫老化 |
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| Outline of Final Research Achievements |
PD-1 signaling negatively regulates immune responses in chronically inflamed liver. We aimed to clarify the pathophysiological role of PD-1-expressing CD4+ and CD8+ T cells in a murine NASH model. Mice were fed HFHC diets for 24 weeks. PD-1-expressing CD4+ and CD8+ T cells were increased in livers of HFHC diet-fed mice in a time-dependent manner related to the degree of hepatic injury. However, PD-1 expression on CD4+ T cells suppressed tumor necrosis factor alpha and interleukin (IL)-6 expression and increased IL-10 expression, and on CD8+ T cells it significantly increased granzyme B and perforin expression despite suppressing IL-6 expression. This regulatory molecule may act as a suppressor in CD4+ T cells, but an activator in CD8+ T cells. Two different effects of PD-1 expression on intrahepatic CD4+ and CD8+ T cells in a murine model of nonalcoholic steatohepatitis, indicating imbalance of cytokine production in PD-1 expressed CD8+ Tcells may be contributed to development of NASH.
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Report
(4 results)
Research Products
(2 results)
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[Presentation] Two different aspects of PD-1 expression on intrahepatic CD4+ and CD8+ T cells in a High Fat High Cholesterol Diet-induced murine NASH.2015
Author(s)
Kanji Yamaguchi, Akira Okajima, Yuya Seko, Hiroshi Ishiba, Hiroyoshi Taketani, Atsushi Umemura, Taichiro Nishikawa, Yoshio Sumida, Hironori Mitsuyoshi, Kohichiroh Yasui, Takeshi Okanoue, Yoshito Itoh.
Organizer
第66回AASLD
Place of Presentation
San Francisco
Year and Date
2015-11-16
Related Report
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