慢性肝损伤引起的肝纤维化最终会发展为肝硬化和肝细胞癌。目前，由于缺乏分子病理学特征，不存在有效的缓解肝纤维化的药物。先前的研究表明，肝脏免疫微环境在肝纤维化的发病机制中起着关键作用，因此巨噬细胞是肝脏中的重要免疫细胞。我们先前的研究发现IDO1在肝免疫微环境中起着重要作用。CRG是一种存在于众多民族药用植物中的没食子酸单宁，具有抗炎症、抗肿瘤和慢性肝病的保护作用。然而，CRG介导IDO1与巨噬细胞在肝免疫成熟过程中的相互作用机制尚不清楚。本研究旨在探究CRG在肝纤维化中的调节机制和IDO1与巨噬细胞分化之间的内在关系。使用斑马鱼、RAW264.7细胞和小鼠进行研究。利用慢病毒技术构建IDO1过表达和敲除细胞系。我们发现CRG明显降低了AST和ALT的血清水平。组织学检查显示，CRG改善了CCL4诱导的肝纤维化，抑制了α-SMA、Lamimin、Collagen-Ι和纤维连接蛋白的表达。此外，我们还发现CRG促进了部分巨噬细胞中MerTK表达的增加。有趣的是，在体外实验中，我们发现CRG抑制IDO1的表达，通过上调CD86、CD80和iNOS，下调CD206、CD163、IL-4和IL-10的表达，从而调节巨噬细胞分化。此外，我们还发现CRG可以通过直接或间接作用抑制肝星状细胞的活化。我们的研究结果表明，CRG通过介导IDO1介导的M2巨噬细胞极化缓解了肝纤维化。版权所有©2023。Elsevier GmbH出版。

Liver fibrosis caused by chronic liver injury, eventually develops into liver cirrhosis and hepatocellular carcinoma. Currently, there are no effective drugs to relieve liver fibrosis due to the lack of molecular pathogenesis characteristics. Former research demonstrates that the hepatic immune microenvironment plays a key role in the pathogenesis of liver fibrosis, thus macrophages are important immune cells in the liver. Our previous study has found that IDO1 plays an important role in the liver immune microenvironment. CRG is a gallic acid tannin found in medicinal plants of many ethnicities that protects against inflammation, tumors and chronic liver disease. However, the mechanism of by which CRG mediates the interaction of IDO1 with macrophages during hepatic immune maturation is not clear.To investigate the regulatory mechanism of CRG in liver fibrosis and the intrinsic relationship between IDO1 and macrophage differentiation.Zebrafish, RAW264.7 cells and mice were used in the study. IDO1 overexpression and knockdown cell lines were constructed using lentiviral techniques.We discovered that CRG remarkably reduced the AST and ALT serum levels. Histological examination revealed that CRG ameliorates CCL4-induced liver fibrosis and depressed the expression of α-SMA, Lamimin, Collagen-Ι and fibronectin. Besides, we found that CRG promoted increased MerTK expression on partly macrophages. Interestingly, in vitro, we found that CRG suppressed IDO1 expression and regulated macrophage differentiation by upregulating CD86, CD80 and iNOS, while downregulating CD206, CD163, IL-4 and IL-10 expression. Additionally, we found that CRG could inhibit hepatic stellate cell activation by direct or indirect action.Our findings suggest that CRG alleviates liver fibrosis by mediating IDO1-mediated M2 macrophage repolarization.Copyright © 2023. Published by Elsevier GmbH.