A new study, published in the journal Gastroenterology, has identified a cellular mechanism causing inflammatory changes in regulatory T cells that can lead to severe viral hepatitis. Research on this mechanism will help further understand the nature of various inflammatory diseases and lead to the development of relevant clinical treatments.
It is known that activated immune cells of patients with viral hepatitis destroy hepatocyte, but its regulatory mechanism has not yet been described. Regulatory T cells inhibit activation of other immune cells and thus are important for homeostasis of the immune system.
However, recent studies contradictorily show that immune inhibitory functions of regulatory T cells weaken in inflammatory conditions and the cells secrete inflammatory cytokines in response. Meanwhile, such a phenomenon was not observed in viral hepatitis including types A, B, and C.
A KAIST immunology research team led by Professors Eui-Cheol Shin and Min Kyung Jung at the Graduate School of Medical Science & Engineering conducted a translational research with teams from Chungnam National University and Yonsei University to identify the mechanism in humans, instead of using animal models.
The team focused on changes in regulatory T cells in patients with viral hepatitis and discovered that regulatory T cells undergo inflammatory changes to secrete inflammatory cytokines (protein secreted by immune cells) called TNF. They also proved regulatory T cells that secrete TNF contributes to the progression of viral hepatitis.
The team confirmed that regulatory T cells of acute hepatitis A patients have reduced immune-inhibitory functions. Instead, their regulatory T cells secrete TNF. Through this research, the team identified a molecular mechanism for changes in regulatory T cells and identified the transcription factor regulating the process. Furthermore, the team found similar changes to be also present in hepatitis B and C patients.
"This is the first research on regulatory T cells that contribute to hepatocyte damage in viral hepatitis," said Professor Shin. "It is significant for identifying the cells and the molecules that can be used as effective treatment targets for viral hepatitis in the future.