| 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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| 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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