Fig. 1: The liver is an immunological organ.

A (Left) Macroscopic view of the liver: it receives a dual blood supply, with nutrient-rich blood from the portal vein (PV) and oxygenated blood from the hepatic artery (HA); the blood exits through the hepatic vein (HV). (Right) Schematic view of the hepatic lobules: the repeated hexagonal anatomical units of the liver. Each lobule consists of hepatocytes (main parenchymal cells) arranged around a central vein (CV) and is demarcated by a portal triad, containing a PV, an HA, and a bile duct (BD), at each corner. B Schematic view of liver cell subsets under homeostatic conditions. Nonparenchymal cells include immune cells, liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs). The HA and PV converge at the portal triads, and the resulting mixed blood flows through the sinusoids toward the CV, generating gradients of oxygen and nutrients that drive the functional zonation of the parenchyma into three distinct zones: periportal, midlobular, and pericentral. Blood immune cells enter and mix in the sinusoids; some cells may circulate, temporarily patrol the sinusoids and parenchyma, or become tissue-resident. Kupffer cells (KCs), the most abundant immune cell subset involved in homeostasis, reside within the sinusoids in close contact with LSECs and extend protrusions that enable interactions with HSCs (residing in the space of Disse) and hepatocytes. This position enables KCs to recognize antigens and pathogens and maintain immune tolerance. Bone marrow monocyte-derived macrophage subsets can also be found around BDs and CVs. Dendritic cells are located primarily periportally. This figure was created with BioRender (biorender.com)