Authors: Kumiko Nishio Takuya Miyagi Tomohide Tatsumi Kaori Mukai Yoshinobu Yokoyama Teppei Yoshioka Ryotaro Sakamori Hayato Hikita Takahiro Kodama Satoshi Shimizu Minoru Shigekawa Takatoshi Nawa Harumasa Yoshihara Naoki Hiramatsu Hiroyuki Yamanaka Kenichiro Seino Tetsuo Takehara
Publish Date: 2015/03/21
Volume: 50, Issue: 11, Pages: 1124-1133
Abstract
Immune tolerance is maintained in the liver and perturbation of tolerance can lead to immunemediated liver diseases such as autoimmune hepatitis AIH Invariant natural killer T iNKT cells and γδT cells have been shown to maintain immune homeostasis as regulatory cells and to play pathogenic roles in immunemediated diseases as effector cells We hypothesized that iNKT cells and γδT cells are involved in the maintenance of hepatic immune tolerance and immunemediated liver diseaseWe measured liver inflammation and the cytokine profiles of liver mononuclear cells in BALB/c wildtype WT mice and BALB/c Jα18deficient KO mice lacking iNKT cells We also examined the role of γδT cells in AIH using liver tissue from AIH patients and control subjectsSpontaneous liver inflammation hepatocyte damage and antinuclearantibody production occurred in Jα18 KO mice but not in WT mice Furthermore liver mononuclear cells from Jα18 KO mice but not those from WT mice produced interleukin17 IL17 γδT cells were the primary producers of the cytokine and they were more abundant in the livers of Jα18 KO mice than in those of WT mice In Jα18 KO mice the administration of antiγδTcellreceptor antibody abolished liver inflammation hepatocyte damage and IL17 production γδT cells accumulated in the livers of AIH patients but not in those of the control subjects
Keywords: