关键词： AIM2, absent in melanoma 2 ALD, alcohol-related liver disease APCs, antigen-presenting cells CDNs, cyclic dinucleotides DAMPs, damage-associated molecular patterns DCs, dendritic cells ER, endoplasmic reticulum GVHD, graft-versus-host disease HCC, hepatocellular carcinoma HSCs, hepatic stellate cells IFN-I, type I interferon IL, interleukin IRF3, interferon regulatory factor 3 IRI, ischaemia refusion injury KCs, Kupffer cells LSECs, liver sinusoidal endothelial cells MHC, major histocompatibility complex NAFLD, non-alcoholic fatty liver disease NK cells, natural killer cells NPCs, non-parenchymal cells PAMPs, pathogen-associated molecular patterns PD-1, programmed cell death protein-1 PD-L1, programmed cell death protein ligand-1 PPRs, pattern recognition receptors SAVI, STING-associated vasculopathy with onset in infancy STING, stimulator of interferon genes TBK1, TANK-binding kinase 1 TGF-β1, transforming growth factor-β1 TLR, Toll-like receptor TNF, tumour necrosis factor XRCC, X-ray repair cross complementing aHSCT, allogeneic haematopoietic stem cell transplantation cGAMP, cyclic guanosine monophosphate-adenosine monophosphate cGAS, cyclic guanosine monophosphate-adenosine monophosphate synthase cGAS-STING signalling dsDNA, double-strand DNA hepatocellular carcinoma innate immune response liver injury mTOR, mammalian target of rapamycin mtDNA, mitochondrial DNA nonalcoholic fatty liver disease siRNA, small interfering RNA ssRNA, single-stranded RNA viral hepatitis

来  源：   DOI：10.1016/j.jhepr.2021.100324   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
The recently identified novel cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) activates the downstream adaptor protein stimulator of interferon genes (STING) by catalysing the synthesis of cyclic GMP-AMP. This in turn initiates an innate immune response through the release of various cytokines, including type I interferon. Foreign DNA (microbial infection) or endogenous DNA (nuclear or mitochondrial leakage) can serve as cGAS ligands and lead to the activation of cGAS-STING signalling. Therefore, the cGAS-STING pathway plays essential roles in infectious diseases, sterile inflammation, tumours, and autoimmune diseases. In addition, cGAS-STING signalling affects the progression of liver inflammation through other mechanisms, such as autophagy and metabolism. In this review, we summarise recent advances in our understanding of the role of cGAS-STING signalling in the innate immune modulation of different liver diseases. Furthermore, we discuss the therapeutic potential of targeting the cGAS-STING pathway in the treatment of liver diseases.
摘要：
最近鉴定的新型胞质DNA传感器环GMP-AMP合酶（cGAS）通过催化环GMP-AMP的合成激活干扰素基因的下游衔接蛋白刺激物（STING）。这反过来通过释放各种细胞因子引发先天免疫反应，包括I型干扰素.外源DNA(微生物感染)或内源DNA(核或线粒体渗漏)可以充当cGAS配体并导致cGAS-STING信号传导的激活。因此,cGAS-STING通路在感染性疾病中起着至关重要的作用，无菌炎症，肿瘤,和自身免疫性疾病。此外,cGAS-STING信号通过其他机制影响肝脏炎症的进展，如自噬和代谢。在这次审查中,我们总结了我们对cGAS-STING信号传导在不同肝脏疾病的先天免疫调节中的作用的理解的最新进展。此外，我们讨论了靶向cGAS-STING途径治疗肝病的治疗潜力。
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