Chen Li, Kong Desong, Xia Siwei, Wang Feixia, Li Zhanghao, Zhang Feng, Zheng Shizhong
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2022 May 17;13:891069. doi: 10.3389/fphar.2022.891069. eCollection 2022.
Liver fibrosis is a repair process of chronic liver injuries induced by toxic substances, pathogens, and inflammation, which exhibits a feature such as deposition of the extracellular matrix. The initiation and progression of liver fibrosis heavily relies on excessive activation of hepatic stellate cells (HSCs). The activated HSCs express different kinds of chemokine receptors to further promote matrix remodulation. The long-term progression of liver fibrosis will contribute to dysfunction of the liver and ultimately cause hepatocellular carcinoma. The liver also has abundant innate immune cells, including DCs, NK cells, NKT cells, neutrophils, and Kupffer cells, which conduct complicated functions to activation and expansion of HSCs and liver fibrosis. Autophagy is one specific type of cell death, by which the aberrantly expressed protein and damaged organelles are transferred to lysosomes for further degradation, playing a crucial role in cellular homeostasis. Autophagy is also important to innate immune cells in various aspects. The previous studies have shown that dysfunction of autophagy in hepatic immune cells can result in the initiation and progression of inflammation in the liver, directly or indirectly causing activation of HSCs, which ultimately accelerate liver fibrosis. Given the crosstalk between innate immune cells, autophagy, and fibrosis progression is complicated, and the therapeutic options for liver fibrosis are quite limited, the exploration is essential. Herein, we review the previous studies about the influence of autophagy and innate immunity on liver fibrosis and the molecular mechanism to provide novel insight into the prevention and treatment of liver fibrosis.
肝纤维化是由有毒物质、病原体和炎症引起的慢性肝损伤的修复过程，其特征表现为细胞外基质的沉积。肝纤维化的起始和进展严重依赖于肝星状细胞（HSCs）的过度激活。激活的肝星状细胞表达不同种类的趋化因子受体，以进一步促进基质重塑。肝纤维化的长期进展会导致肝脏功能障碍，并最终引发肝细胞癌。肝脏还拥有丰富的固有免疫细胞，包括树突状细胞（DCs）、自然杀伤细胞（NK细胞）、自然杀伤T细胞（NKT细胞）、中性粒细胞和库普弗细胞，它们在肝星状细胞的激活和扩增以及肝纤维化过程中发挥着复杂的功能。自噬是一种特定类型的细胞死亡，通过它异常表达的蛋白质和受损的细胞器被转运到溶酶体进行进一步降解，在细胞稳态中起关键作用。自噬在各个方面对固有免疫细胞也很重要。先前的研究表明，肝脏免疫细胞中的自噬功能障碍可导致肝脏炎症的起始和进展，直接或间接引起肝星状细胞的激活，最终加速肝纤维化。鉴于固有免疫细胞、自噬和纤维化进展之间的相互作用很复杂，且肝纤维化的治疗选择非常有限，因此进行探索至关重要。在此，我们回顾先前关于自噬和固有免疫对肝纤维化影响的研究及其分子机制，为肝纤维化的预防和治疗提供新的见解。
