Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications

Figure 3 Hierarchical framework of stage-specific therapeutic strategies for liver disease progression. Fibrosis progression is organized into bridging, amplification, and locking layers, targeting neutrophil extracellular traps-hepatic stellate cells crosstalk, NOD-like receptor family pyrin domain containing 3 signaling, and transforming growth factor-βR1-driven extracellular matrix/immune exclusion, respectively, enabling stage-specific disruption of inflammation-fibrosis coupling. HSC: Hepatic stellate cell; IL: Interleukin; NET: Neutrophils extracellular trap; TGFβR1: Transforming growth factor-β receptor 1; NLRP3: NOD-like receptor family pyrin domain containing 3; PAD4: Peptidylarginine deiminase 4; PGE2: Prostaglandin E₂; COX-2: Cyclooxygenase-2; HCC: Hepatocellular carcinoma; ECM: Extracellular matrix; ICI: Immune checkpoint inhibitor; MASH: Metabolic dysfunction-associated steatohepatitis; ALD: Alcohol-related liver disease.