Kupffer

Kupffer cells are specialized macrophages located in the liver, lining the walls of the hepatic sinusoids. They are the largest population of resident macrophages in the body and form a key part of the liver’s reticuloendothelial system. Named after Karl Wilhelm von Kupffer, they serve as a frontline defense by filtering bacteria, endotoxins, and debris from portal blood.

Functionally, Kupffer cells perform phagocytosis of bacteria and particulate matter, clear immune complexes and senescent cells, and recycle components such as iron from red blood cells. They secrete a range of cytokines and chemokines in response to pathogens, contributing to inflammation and innate immunity. They also present antigens to T cells, supporting adaptive immune responses, though the liver tends to maintain tolerogenic conditions to prevent excessive reactions to gut-derived antigens. Through scavenger receptors and pattern recognition receptors, including TLRs, they detect microbial products and cellular danger signals. Specific surface markers and receptors, such as CD68, CD163, scavenger receptors (SR-A, MARCO), and, in mice, CLEC4F, characterize Kupffer cells and facilitate their roles in clearance and signaling.

Origin and turnover are distinctive. In development, Kupffer cells arise from yolk sac–derived progenitors and establish self-renewing populations in the liver. In steady state, they maintain numbers through self-renewal, but during injury or inflammation, monocyte-derived cells can replenish the Kupffer cell pool.

Clinical relevance is substantial. Activation of Kupffer cells by gut-derived endotoxins (for example, lipopolysaccharide) drives inflammatory cascades implicated in alcoholic liver disease, nonalcoholic fatty liver disease, and other forms of liver injury. They may also influence liver regeneration and fibrosis through cytokine signaling and interactions with hepatic stellate cells. Understanding their biology informs therapeutic approaches targeting hepatic inflammation and immune tolerance.