Figure 1.

Lymphocyte trafficking in chronic liver disease. Lymphocyte recruitment from the circulation into liver tissue occurs within the low shear specialized channels of the hepatic sinusoids that are lined by hepatic sinusoidal endothelial cells and the macrophage liver resident population, the Kupffer cells. During liver injury, the signals of damaged epithelial cells lead to activation of hepatic stellate cells in the Space of Disse underneath the sinusoidal endothelium. The sinusoidal endothelium itself is activated and upregulates the expression of adhesion molecules, which promote the recruitment of lymphocytes from circulation in an organ specific manner. This involves an adhesion cascade where lymphocytes in circulation undergo a tethering step leading to firm adhesion and activation on the endothelial surface, followed by their transendothelial migraton into liver tissue.