Abstract
Liver fibrosis, a hallmark pathological endpoint of chronic aging-related liver diseases, remains a clinical challenge with limited therapeutic options. In healthy liver, myeloid cells constitute <5% of total hepatic immune cells, primarily comprising tissue-resident Kupffer cells. However, during aging or chronic injury, bone marrow-derived myeloid cell recruitment increases by two- to threefold in murine fibrotic models, reaching 15%-20% of intrahepatic immune populations. These infiltrating myeloid subsets exhibit functional plasticity, dynamically differentiating into pro-inflammatory macrophages or fibrosis-promoting Kupffer-like cells, contingent upon chemokine gradients (e.g., CCL2/CCR2 axis) and damage-associated molecular patterns (DAMPs). This review systematically examines the regulatory mechanisms of myeloid cells in liver fibrogenesis, with particular emphasis on their developmental origins, hepatic recruitment dynamics, functional heterogeneity, and pathogenic contributions to fibrosis. Furthermore, signaling pathways involving myeloid cells in liver fibrosis and therapeutic approaches modulating their differentiation and recruitment are discussed in this review.