Natural killer T cells in liver injury, inflammation and cancer

Abstract

The liver is an organ that has the largest amount of natural killer T(NKT) cells, which play critical roles in the pathogenesis of liver diseases. In this article, the authors summarize recent findings about the roles of NKT cells in liver injury, inflammation, fibrosis, regeneration and cancer. In brief, NKT cells accelerate liver injury by producing pro-inflammatory cytokines and directly killing hepatocytes. NKT cells are involved in complex roles in liver fibrogenesis. For instance, NKT cells inhibit liver fibrosis via suppressing hepatic stellate cell activation and can also promote liver fibrosis via enhancing liver inflammation and injury. Inactivated or weakly activated NKT cells play a minimal role in controlling liver regeneration, whilst activated NKT cells have an inhibitory effect on liver regeneration. In liver cancer, NKT cells play both pro-tumor and anti-tumor roles in controlling tumor progress.

Keywords:

• liver cancer
• liver fibrosis
• liver injury
• liver regeneration
• NKT cells

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (grant number: 81100311, 81470879/H0318 to S Yin; grant number 81372577/H1617 to H Wang), the New Century Excellent Talents in University, Ministry of Education of China (grant number: NCET-13 - 0644 to H. Wang) and Wanjiang Scholars Program of Anhui Province of China (to H Wang). The authors would like to thank Dr. Teresa Ramirez from Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, for critical reading of this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Key issues

• The liver is the organ with the highest number of natural killer T(NKT) cells, which play critical roles in the pathogenesis of liver diseases.

• NKT cells accelerate liver injury by producing proinflammatory cytokines and killing hepatocytes directly.

• NKT cells play complex roles in liver fibrogenesis. On the one hand, NKT cells inhibit liver fibrosis via suppressing hepatic stellate cell activation. On the other hand, NKT cells promote liver fibrosis via enhancing liver inflammation and injury.

• Inactivated or weakly activated NKT cells play a minimal role in controlling liver regeneration while activated NKT cells have an inhibitory effect on liver regeneration.

• In liver cancer, NKT cells play both pro-tumor and anti-tumor roles in controlling tumor progress.