Chemokine-directed immune cell infiltration in acute and chronic liver disease

Abstract

The infiltration of various immune cell populations, including monocytes/macrophages, natural killer (NK), NKT cells and T cells, is a central pathogenic feature following acute- and chronic liver injury. Chemotactic cytokines, chemokines, are small-protein mediators that direct the migration of immune cells. Several hepatic cell populations, including hepatocytes, Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells, can secrete chemokines upon activation. Samples from liver-disease patients and animal models of experimental injury highlight multiple activated chemokine pathways during initiation, maintenance or resolution of liver pathology. Monocyte chemoattractant protein-1 (Chemokine [C-C motif] ligand [CCL]2) can attract monocytes via CCR2. Infiltrating monocytes probably have functions in both disease progression and resolution of damage. RANTES (CCL5) may promote infiltration of NK (via CCR1) and T cells (via CCR5). Dissecting the exact functional contribution of immune cell subsets, chemokines and chemokine-receptor pathways in liver injury will hopefully identify novel targets for the treatment of acute liver failure, liver fibrosis or cirrhosis.