Interleukin (IL)-17-producing CD4+ T cells (Th17) have been shown to play crucial roles in the pathogenesis of hepatitis B virus (HBV)-associated acute-on-chronic liver failure.
However, the mechanism underlying the enhanced Th17 responses in these patients remains elusive.
Dr Hee Yeon Kim and colleagues evaluated the relevance of the IL-6/signal transducer and activator of transcription 3 (STAT3)/mammalian target of rapamycin (mTOR)/Th17 loop in HBV-associated acute-on-chronic liver failure.
The team enrolled 8 patients with HBV-associated acute-on-chronic liver failure, 8 asymptomatic chronic HBV carriers, and 8 healthy controls.
The frequency of peripheral Th17 cells was determined by flow cytometry.
|The percentage of peripheral Th17 cells significantly increased in acute-on-chronic liver failure|
|Journal of Gastroenterology|
IL-17 and IL-6 mRNA levels in peripheral blood mononuclear cells were quantified using quantitative real-time reverse polymerase chain reaction.
The team observed the activation of STAT3 upon stimulation with IL-6.
Rapamycin, an mTOR inhibitor, was used for analysis of the suppressive effect on the Th17 response in vitro.
The team found that the percentage of peripheral Th17 cells significantly increased in acute-on-chronic liver failure patients.
CD4+ T cells from acute-on-chronic liver failure patients produced higher levels of IL-17 and IL-6 upon stimulation in vitro.
The researchers noted that the activation of STAT3 in response to IL-6 was elevated in acute-on-chronic liver failure patients.
The IL-6-induced upregulation of IL-17 production by CD4+ T cells could be reversed by an mTOR inhibitor through decreasing STAT3 activation.
Dr Kim's team concludes, "STAT3 activation upon IL-6 stimulation contributed to the enhanced Th17 response in HBV-associated acute-on-chronic liver failure patients and mTOR regulated STAT3 phosphorylation."
"mTOR can be a novel target to suppress Th17-mediated liver injury in HBV-associated acute-on-chronic liver failure patients."