SCARF-1 mediates recruitment of CD4+ T cells to the hepatic sinusoidal endothelium: a new player in the gut-liver axis?

Scavenger receptors are able to bind a diverse range of both endogenous and exogenous antigens; consequently, they play an important role in tissue homeostasis and also contribute to the pathophysiology of a wide range of... [ view full abstract ]

Scavenger receptors are able to bind a diverse range of both endogenous and exogenous antigens; consequently, they play an important role in tissue homeostasis and also contribute to the pathophysiology of a wide range of inflammatory diseases, including a range of liver diseases. Liver sinusoidal endothelial cells are constantly exposed to gut-derived antigens and, as a consequence, express a unique repertoire of scavenger receptors. Whilst there is increasing evidence that the gut contributes to chronic inflammatory liver disease, the role of liver-expressed scavenger receptors in regulating hepatic inflammation remains limited. Here, we describe for the first time the expression of scavenger receptor class F, member 1 (SCARF-1) in normal human liver tissue and its up-regulation in chronic liver disease. We report that hepatic sinusoidal endothelial cells (HSEC) are the predominant source of hepatic SCARF-1 and that the expression on isolated primary HSEC is regulated in the presence of proinflammatory cytokines and bacterial products. Furthermore, expression of SCARF-1 by HSEC, following treatment with proinflammatory and gut-derived factors, acts as a novel adhesion molecule that specifically supports CD4 T cells under conditions which mimic physiological shear stress. In conclusion, we show that SCARF-1 contributes to lymphocyte subset-specific recruitment to the liver and could play an important role in regulating the inflammatory response during chronic liver disease.