Increased PD‐L1 Restricts Liver Injury in Nonalcoholic Fatty Liver Disease
Gang Dong, Xiaoquan Huang, Rongxin Chen, Ling Wu, Siyu Jiang, Shiyao Chen
Abstract
PD‐L1 is a critical checkpoint that protects tissues from autoimmune injury. Nevertheless, the role of PD‐L1 in nonalcoholic fatty liver disease‐ (NAFLD‐) induced liver damage is still unclear. In this study, we examined the role and mechanism of PD‐L1 expression on NAFLD‐induced liver damage in vitro and in vivo. PD‐L1 expression in the livers from patients with NAFLD, and LO2 cells treated by FFA, was significantly increased. FFA triggers a large amount of ROS (generated from NOX4 and damaged mitochondria), promoting the ZNF24 expression and suppressing ZN24 sumoylation, both of which enhance the PD‐L1 transcription and expression. The knockdown of PD‐L1 increases CD8 + T cells’ damage to FFA‐treated LO2 cells, while its upregulation limits the liver injury in NAFLD models. Collectively, we demonstrate that FFA promotes PD‐L1 expression through the ROS/ZNF24 pathway and suppresses UBE2I‐mediated ZNF24 sumoylation to enhance its transcriptional activity of PD‐L1. PD‐L1 upregulation limits FFA‐induced injury of hepatocytes in vitro and in vivo .