Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically
Abstract
:1. Introduction
1.1. Complications of Liver Regeneration Therapeutics
1.2. Initiation of Liver Fibrosis
2. Immunopathology of Liver Fibrosis
2.1. Innate Immune Cells
2.2. Adaptive Immune Cells
3. Regulatory T Cells
3.1. Tregs as Potential Inducers of Liver Fibrosis
3.2. Potential Role of Tregs in the Attenuation of Liver Fibrosis
3.3. Tregs: Pro-Fibrotic or Protective?
4. Immunotherapy of Liver Fibrosis
4.1. Clinical Potential of CAR T Cells
4.2. Treg Manipulation as a Next-Generation Therapy
5. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Authorship, Year, Title | Model | Study Findings | Ref. |
---|---|---|---|
Zhao, X. et al. (2013) Endothelial cells overexpressing IL-8 receptor reduce cardiac remodelling following myocardial infarction. | Myocardial infarction model induced by left anterior descending coronary artery ligation in male Sprague-Dawley rats. | Cell-based therapy was able to indirectly reduce fibrosis by decreasing inflammatory cell infiltration by reducing IL-8-mediated pro-inflammatory responses. This may be possible to apply to liver fibrosis models. | [132] |
Abe, H. et al. (2016) Effective prevention of liver fibrosis by liver-targeted hydrodynamic gene delivery of matrix metalloproteinase-13 in a rat liver fibrosis model. | Liver fibrosis model induced by bile duct ligation in female Wistar rats. | Liver-targeted delivery of MMP13 gene led to decreased levels of hyaluronic acid and a decreased volume of fibrotic tissue, thus may be an effective antifibrotic genetic therapeutic for preventing liver fibrosis progression. | [134] |
Kim, E.-J. et al. (2011) Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid. | CCl4-induced murine model of liver fibrosis. | Administration of plasmid DNA encoding MMP13 (pMMP13) resulted in increased expression of MMP13 and reduced collagen I deposition in liver tissue with the potential to ameliorate collagen deposition and support fibrosis recovery. | [135] |
He, B. et al. (2017) The imbalance of Th17/Treg cells is involved in the progression of non-alcoholic fatty liver disease in mice. | Murine model (C57BL/6 mice) of NAFLD. | High-fat-fed mice had a higher frequency of intrahepatic Th17 cells, and lower frequencies of Tregs compared to a normal diet. Use of polyene phosphatidylcholine capsules demonstrated the ability to restore the Treg/Th17 ratio cell balance to reduce inflammation and thus fibrosis within the liver. | [136] |
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Lowe, K.O.; Tanase, C.E.; Maghami, S.; Fisher, L.E.; Ghaemmaghami, A.M. Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically. Immuno 2023, 3, 375-408. https://doi.org/10.3390/immuno3040023
Lowe KO, Tanase CE, Maghami S, Fisher LE, Ghaemmaghami AM. Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically. Immuno. 2023; 3(4):375-408. https://doi.org/10.3390/immuno3040023
Chicago/Turabian StyleLowe, Kirstin O., Constantin E. Tanase, Susan Maghami, Leanne E. Fisher, and Amir M. Ghaemmaghami. 2023. "Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically" Immuno 3, no. 4: 375-408. https://doi.org/10.3390/immuno3040023