Kupffer cells (KCs) are liver-resident macrophages with several key roles in maintaining healthy liver function. As phagocytes, their main function is to engulf bacterial pathogens and endotoxins, dead cells, microbial debris and other antigens in the liver. In this way, they help to protect the liver from infections and at the same time prevent unnecessary immune activation against harmless antigens.
What is a Kupffer cell?
Kupffer cells (AKA hepatic macrophages) are a type of macrophage found in liver tissue. They make up 80-90% of the total number of macrophages in the immune system and play a vital role in maintaining healthy liver function.
Development of Kupffer cells
The lifespan and renewal mechanisms of Kupffer cells are still being discussed by scientists. A popular hypothesis is that like other immune system cells, KCs develop from stem cells in the bone marrow before they migrate to the liver. Other researchers believe that KCs are capable of self-renewal and develop from the division of cells in the liver.
KCs are thought to live around 3.8 days, although some studies have shown that these cells can last up to 14 months in rats.
Function of Kupffer cells
Kupffer cells are macrophages and part of the innate immune system. They have a variety of functions in the liver, including phagocytosis of pathogens, antigen presentation, and immunosuppression.
Like all macrophages are KCs Phagocytes which engulf and digest pathogens, immune complexes, lysosomes, tumor cells, endotoxins and more.
Their main function is to protect the liver from infection, and KCs quickly clear bacteria, endotoxins, and other microbial debris that enter the bloodstream from the gastrointestinal tract. They also engulf and destroy dead cells in the liver after inflammation or tissue injury, which helps maintain liver homeostasis.
Kupffer cells function as antigen presenting cells (APCs) in the liver and express low levels of both the MHC I and MHC II complexes. As soon as they have devoured a pathogen, they present its antigens as part of the MHC complex and present it to resident T cells. KCs can induce the activation and proliferation of T cells in the liver and thus induce an adaptive immune response.
One of the most important functions of the Kupffer cells is to promote immune tolerance in the liver. The liver is constantly exposed to a constant flow of antigens from the intestine and small amounts of bacterial endotoxins. By engulfing and destroying non-threatening antigens, KCs help prevent unnecessary immune activation.
KCs also secrete PGE2 and IL-10, two immunosuppressive products that downregulate the antigen-presenting functions of other immune cells in the liver. This helps to inhibit the activation of effector T cells and therefore suppresses the immune response against antigens.
Finally, KCs play an important role in activating regulatory T cells (Tregs). Tregs regulate and suppress immune function by helping to prevent the activation and proliferation of effector T cells (namely, helper T cells and cytotoxic T cells). They are also thought to suppress the functions of B cells and dendritic cells. In doing so, they dampen the immune response to antigens in the liver.
Kupffer cells and alcohol-induced liver disease
Kupffer cells are known to play a role in the development of alcohol-induced liver disease, although the exact mechanism by which they do so is not fully understood. One theory suggests that excessive alcohol consumption decreases the ability of KCs to clear bacterial endotoxins from the liver, resulting in higher blood levels. Another proposed theory is that alcohol consumption increases the absorption of endotoxins through the intestinal wall, resulting in higher levels of endotoxins in the blood.
KCs are activated when they internalize these endotoxins, resulting in the production of reactive oxygen species (ROS). These increase oxidative stress in the liver, which leads to liver damage and ultimately loss of liver function.