Immunology in the liver — from homeostasis to disease

The liver is a central immunological organ with a high density of myeloid (such as Kupffer cells, neutrophils or macrophages) and lymphoid (such as natural killer cells, T cells or B cells) immune cellsAs antigen-rich blood from the gastrointestinal tract and gut-derived endotoxins pass through the sinusoids, many mechanisms in homeostasis ensure suppression of innate and adaptive immune responses, resulting in toleranceIn conditions of hepatic diseases, conserved mechanisms such as molecular danger patterns (alarmins), Toll-like receptor signalling or inflammasome activation initiate inflammatory responses, resulting in the chemokine-mediated hepatic infiltration of circulating leukocytesKupffer cells and monocyte-derived macrophages adapt their phenotype to local signals and exert critical functions in perpetuating inflammation and wound healing, but can also mediate resolution of inflammation and fibrosisInnate lymphocytes (for example, natural killer and natural killer T cells) are another source of immunoregulatory cytokines in diseased livers and furthermore contribute to eliminating activated myofibroblasts and infected, injured or malignant cellsThe heterogeneous pool of hepatic T cells is activated towards immunity upon injury, resulting in immune-stimulatory cytokine secretion as well as direct cytopathic functions, especially in viral and autoimmune hepatitis