Figure 1
Monocyte subsets in experimental liver fibrosis in mice. Upon liver injury, hepatocytes, hepatic stellate cells, endothelium and resident macrophages (Kupffer cells) release many cytokines and chemokines (not shown in detail). CCL2 is an important mediator that promotes the accumulation of inflammatory CCR2+ Ly6Chi (Gr1hi) monocytes from blood into the injured liver. CCR8 and its ligand CCL1 also promote monocyte/macrophage migration in hepatic fibrosis. Intrahepatic monocytes develop preferentially into 'M1' inflammatory macrophages in this setting. These monocytes/macrophages release proinflammatory cytokines such as TNFα, IL1β or IL6 that further promote hepatocyte apoptosis, hepatocyte steatosis and inflammation, but also directly interact with hepatic stellate cells via TGFβ, thereby contributing to myofibroblast transdifferentiation and collagen production. CX3CL1-CX3CR1 interactions on monocytes/macrophages are anti-inflammatory and anti-fibrotic by prolonging monocyte survival and limiting M1 macrophage differentiation.