Fig. 2.

The acute response to sterile injury in the liver. During liver injury, hepatocyte death causes DAMP release, resulting in Kupffer cell activation, neutrophil recruitment to the site of injury and the activation of hepatic stellate cells, leading to cytokine secretion. Kupffer cells and neutrophils release inflammatory mediators and begin to phagocytose necrotic debris. T cells, dendritic cells, and Kupffer cells facilitate leukocyte infiltration from the systemic circulation by releasing chemoattractants such as CCL2 and IL-17. NK and NKT cells release IFNγ, stimulating the release of proinflammatory mediators. During resolution, monocytes acquire a reparative phenotype, and macrophage reprogramming occurs in a subset of macrophages that exhibit a resolution phenotype. Monocytes migrate across the liver sinusoidal endothelial cell layer, differentiating into macrophages to either replenish the Kupffer cell pool or restore homeostasis by secreting anti-inflammatory cytokines and promoting angiogenesis. Following injury, a restorative macrophage phenotype emerges, promoting neutrophil apoptosis. Hepatocyte proliferation occurs to replace the lost parenchyma¹³¹