Alessandra Warren completed her PhD entitled, “Hepatic sinusoidal cells in liver immunology and ageing” in 2006. Part of her work focused on understanding a key issue in immune-mediated liver disease: how T lymphocytes interact with hepatocytes in the presence of a sinusoidal endothelial cell barrier.

Electron microscopy studies of a murine model, in collaboration with Dr Patrick Bertolino from the Centenary Institute of Cancer Medicine and Cell Biology (Sydney) , demonstrated that intrahepatic and naive T lymphocytes present cytoplasmic extensions which protrude through sinusoidal cell fenestrations and contact hepatocyte’s microvilli. Moreover, fenestrations appear to be important for infiltration of inflammatory cells from the circulation into the parenchyma during autoimmune-hepatitis. These findings suggest that hepatic sinusoidal endothelial cell fenestrations have an important role in liver immunology leading to future studies on their therapeutical implications.

Further work was undertaken at University of Tromso (Norway) studying endocytosis of bacterial antigens by hepatic sinusoidal endothelial cells.