STING and liver disease

• Published in: Journal of gastroenterology 2021-08, Vol.56 (8), p.704-712
• Main Authors: Chen, Can, Yang, Rui-Xia, Xu, Hua-Guo
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adaptive immunity; Biological response modifiers; Cell activation; Cell proliferation; Colorectal Surgery; Connective tissues; Cytokines; Dendritic cells; Development and progression; Disease susceptibility; Gastroenterology; Health aspects; Hepatitis; Hepatitis C - complications; Hepatocellular carcinoma; Hepatocytes; Hepatology; Homeostasis; Humans; Immune response; Inflammation; Innate immunity; Interferon; Interferon regulatory factor 3; Kupffer cells; Liver cancer; Liver diseases; Liver Diseases - genetics; Lymphocytes T; Macrophages; Medicine; Medicine & Public Health; Membrane Proteins - pharmacology; Metabolic disorders; Metabolism; Metastases; NF-κB protein; Review; Signal Transduction - drug effects; Stellate cells; Surgical Oncology; T cells; Tumorigenesis; Virus diseases
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-021-01803-1

STING (stimulator of interferon genes) also known as transmembrane protein 173 (TMEM173) is a cytoplasmic DNA sensor which can be activated by the upstream cyclic dinucleotides (CDNs). This activation produces cytokines such as interferons and pro-inflammatory factors via the downstream IRF3 and NF-κB pathways, triggering an innate immune response and adaptive immunity to maintain homeostasis. STING is mainly expressed and activated in non-parenchymal cells, thus exerting a corresponding effect to maintain the homeostasis of the liver. In viral hepatitis, interferons and pro-inflammatory factors produced after STING activation initiate the immune response to inhibit virus replication and assembly. In the case of metabolic diseases of the liver, the activation of STING in kupffer cells and hepatic stellate cells leads to inflammation, the proliferation of connective tissue, and metabolic disorders in the hepatocytes, promoting the occurrence and development of the disease. In hepatocellular carcinoma, STING has two contradictory roles. When STING is activated in dendritic cells and macrophages, a large number of cytokines can be produced to initiate innate immune effects directly and to exert adaptive immunity through the recruitment and activation of T cells; however, aberrant activation of the STING pathway leads to a weakening of immune function and promotes oncogenesis and metastasis. Here, we summarize the interactions between STING and liver disease that have currently been identified and how to achieve therapeutic goals by modulating the activity of the STING pathway.