STING Activation in Various Cell Types in Metabolic Dysfunction-Associated Steatotic Liver Disease

Abstract

Background

During the hepatic histological progression in metabolic dysfunction-associated steatotic liver disease (MASLD), the immunological mechanisms play a the pivotal role, especially when progressing to metabolic dysfunction-associated steatohepatitis (MASH). The discovery of the stimulator of interferon genes (STING) marked a significant advancement in understanding the immune system.

Methods

We searched literature on STING involved in MASLD in PubMed to summarise the role of intrahepatic or extrahepatic STING signal pathways and the potential agonists or inhibitors of STING in MASLD.

Results

Besides inflammation and type I interferon response induced by STING activation in the intrahepatic or extrahepatic immune cells, STING activation in hepatocytes leads to protein aggregates and lipid deposition. STING activation in hepatic macrophages inhibits autophagy in hepatocytes and promotes hepatic stellate cells (HSCs) activation. STING activation in HSCs promotes HSC activation and exacerbates liver sinusoidal endothelial cells (LSECs) impairment. However, it was also reported that STING activation in hepatic macrophages promotes lipophagy in hepatocytes and STING activation in HSCs leads to HSC senescence. STING activation in LSEC, inhibits angiogenesis. For extrahepatic tissue, STING signalling participates in the regulation of the intestinal permeability, intestinal microecology and insulin action in adipocytes, which were all involved in the pathogenesis of MASLD.

Conclusion

There're plenty of STING ligands in MASLD. How STING activation affects the intercellular conversation in MASLD deserves thorough investigation.