Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity

Liver sinusoidal endothelial cells (LSECs) line the low shear, sinusoidal capillary channels of the liver and are the most abundant non-parenchymal hepatic cell population. LSECs do not simply form a barrier within the hepatic sinusoids but have vital physiological and immunological functions, including filtration, endocytosis, antigen presentation and leukocyte recruitment. Reflecting these multifunctional properties, LSECs display unique structural and phenotypic features that differentiate them from the capillary endothelium present within other organs. It is now clear that LSECs have a critical role in maintaining immune homeostasis within the liver and in mediating the immune response during acute and chronic liver injury. In this Review, we outline how LSECs influence the immune microenvironment within the liver and discuss their contribution to immune-mediated liver diseases and the complications of fibrosis and carcinogenesis. Liver sinusoidal endothelial cells (LSECs) represent the most abundant non-parenchymal hepatic cell population. In this Review, the authors explore the key roles that LSECs have in regulating hepatic immunity and their contribution to immune-mediated disease, liver fibrosis and carcinogenesis. Key points Liver sinusoidal endothelial cells (LSECs) that line the hepatic sinusoids have important physiological roles and mediate the filtration and scavenger functions of the liver. LSECs also have innate and adaptive immunological functions, including antigen presentation and maintenance of the balance between tolerance and effector immune responses. In inflammatory liver diseases, LSECs influence the composition of hepatic immune populations by mediating diapedesis of leukocyte subsets via distinct combinations of adhesion molecules and chemokines. LSECs play a crucial part in the cellular crosstalk that regulates progressive chronic liver disease, which leads to fibrosis and carcinogenesis. The role of LSECs in initiating immune responses and contributing to progressive liver disease makes them a potential therapeutic target for treating inflammatory liver diseases.