The cGAS-STING Pathway: Novel Perspectives in Liver Diseases
Liver diseases represent a major global health burden accounting for approximately 2 million deaths per year worldwide. The liver functions as a primary immune organ that is largely enriched with various innate immune cells, including macrophages, dendritic cells, neutrophils, NK cells, and NKT cell...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.682736/full |
| _version_ | 1818647907104980992 |
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| author | Dongwei Xu Dongwei Xu Yizhu Tian Qiang Xia Bibo Ke |
| author_facet | Dongwei Xu Dongwei Xu Yizhu Tian Qiang Xia Bibo Ke |
| author_sort | Dongwei Xu |
| collection | DOAJ |
| description | Liver diseases represent a major global health burden accounting for approximately 2 million deaths per year worldwide. The liver functions as a primary immune organ that is largely enriched with various innate immune cells, including macrophages, dendritic cells, neutrophils, NK cells, and NKT cells. Activation of these cells orchestrates the innate immune response and initiates liver inflammation in response to the danger signal from pathogens or injured cells and tissues. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial signaling cascade of the innate immune system activated by cytosol DNA. Recognizing DNA as an immune-stimulatory molecule is an evolutionarily preserved mechanism in initiating rapid innate immune responses against microbial pathogens. The cGAS is a cytosolic DNA sensor eliciting robust immunity via the production of cyclic GMP-AMPs that bind and activate STING. Although the cGAS-STING pathway has been previously considered to have essential roles in innate immunity and host defense, recent advances have extended the role of the cGAS-STING pathway to liver diseases. Emerging evidence indicates that overactivation of cGAS-STING may contribute to the development of liver disorders, implying that the cGAS-STING pathway is a promising therapeutic target. Here, we review and discuss the role of the cGAS-STING DNA-sensing signaling pathway in a variety of liver diseases, including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), primary hepatocellular cancer (HCC), and hepatic ischemia-reperfusion injury (IRI), with highlights on currently available therapeutic options. |
| first_indexed | 2024-12-17T01:09:59Z |
| format | Article |
| id | doaj.art-9b367c9b61704a1b8d4888ed7a6812a0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T01:09:59Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9b367c9b61704a1b8d4888ed7a6812a02022-12-21T22:09:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.682736682736The cGAS-STING Pathway: Novel Perspectives in Liver DiseasesDongwei Xu0Dongwei Xu1Yizhu Tian2Qiang Xia3Bibo Ke4The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesLiver diseases represent a major global health burden accounting for approximately 2 million deaths per year worldwide. The liver functions as a primary immune organ that is largely enriched with various innate immune cells, including macrophages, dendritic cells, neutrophils, NK cells, and NKT cells. Activation of these cells orchestrates the innate immune response and initiates liver inflammation in response to the danger signal from pathogens or injured cells and tissues. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial signaling cascade of the innate immune system activated by cytosol DNA. Recognizing DNA as an immune-stimulatory molecule is an evolutionarily preserved mechanism in initiating rapid innate immune responses against microbial pathogens. The cGAS is a cytosolic DNA sensor eliciting robust immunity via the production of cyclic GMP-AMPs that bind and activate STING. Although the cGAS-STING pathway has been previously considered to have essential roles in innate immunity and host defense, recent advances have extended the role of the cGAS-STING pathway to liver diseases. Emerging evidence indicates that overactivation of cGAS-STING may contribute to the development of liver disorders, implying that the cGAS-STING pathway is a promising therapeutic target. Here, we review and discuss the role of the cGAS-STING DNA-sensing signaling pathway in a variety of liver diseases, including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), primary hepatocellular cancer (HCC), and hepatic ischemia-reperfusion injury (IRI), with highlights on currently available therapeutic options.https://www.frontiersin.org/articles/10.3389/fimmu.2021.682736/fullDNA sensorcyclic GMPAMP synthasestimulator of interferon genesInnate immunityinflammationliver diseases |
| spellingShingle | Dongwei Xu Dongwei Xu Yizhu Tian Qiang Xia Bibo Ke The cGAS-STING Pathway: Novel Perspectives in Liver Diseases Frontiers in Immunology DNA sensor cyclic GMPAMP synthase stimulator of interferon genes Innate immunity inflammation liver diseases |
| title | The cGAS-STING Pathway: Novel Perspectives in Liver Diseases |
| title_full | The cGAS-STING Pathway: Novel Perspectives in Liver Diseases |
| title_fullStr | The cGAS-STING Pathway: Novel Perspectives in Liver Diseases |
| title_full_unstemmed | The cGAS-STING Pathway: Novel Perspectives in Liver Diseases |
| title_short | The cGAS-STING Pathway: Novel Perspectives in Liver Diseases |
| title_sort | cgas sting pathway novel perspectives in liver diseases |
| topic | DNA sensor cyclic GMPAMP synthase stimulator of interferon genes Innate immunity inflammation liver diseases |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.682736/full |
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