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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
