Interactions between hepatic stellate cells and immune cells: Implications for liver fibrosis

Liver fibrosis is a chronic disease leading to hepatocellular carcinoma and liver failure, posing a major global health challenge. Hepatic stellate cells (HSCs) differentiate into myofibroblasts, central to fibrosis progression, but current therapies targeting fibrotic pathways are inadequate. Evidence highlights the critical role of bidirectional crosstalk between HSCs and immune cells in dynamically regulating fibrosis, offering new immunomodulatory targets. This review explores how immune cells, including macrophages, neutrophils, dendritic cells (DCs), T and B lymphocytes, and natural killer cells (NK cells), coordinate HSC activation through cytokines, receptors, and feedback signals, shaping immune phenotypes. The dual role of immune regulation is emphasized: pro-fibrotic during injury, anti-fibrotic during remission. Emerging therapeutic strategies, including gut-liver axis modulation and engineered exosomes, show promising yet preliminary potential for precise fibrosis treatment. By integrating immunoregulatory networks governing HSC-immune interactions, this work provides a roadmap for developing precision therapies to combat fibrosis by harnessing the hepatic immune microenvironment's plasticity. We decipher how these strategies modulate immune cell function and the microenvironment to regulate HSCs activation, offering new therapeutic avenues with promising potential.