Examination about the association between intrahepatic immunogenicity and the expression of regulatory molecules on hepatic T cells in mouse NASH model.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YAMAGUCHI KANJI 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50381950)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 脂肪肝炎

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.

Free Research Field

消化器内科