Table 3.
The crosstalk of hepatic macrophages with other cells in the liver.
| Interacted cell types | Roles of hepatic macrophages in interaction | Reported in liver diseases | References | |
|---|---|---|---|---|
| KCs | Hepatocytes | KCs activate Notch signaling in hepatocytes | ICC | (81) |
| Hepatocytes | KCs are essential for proliferation of liver progenitor cells | Choline-deficient, ethionine-supplemented diet-mediated liver injury | (82) | |
| Hepatocytes | KCs trigger hepatocytes senescence | ALD | (83) | |
| Hepatocytes | KC are activated by hepatocytes-derived extracellular vesicles | ALD | (84, 85) | |
| HSCs | KCs activate HSCs and modulate fibrogenic responses in HSCs | Liver fibrosis | (86, 87) | |
| HSCs | KCs secrete IFN-γ to induce apoptosis of HSCs | Liver fibrosis | (88) | |
| HSCs | HSCs induce KCs differentiation and decrease its cytokine secretion | Liver fibrosis | (89) | |
| LSECs | KCs are essential for LSECs' uptake of hyaluronic acid | In vitro culture | (90) | |
| MoMϕs | KCs produce CCL2 to recruit MoMϕs | Amodiaquine-induced liver injury | (91) | |
| Neutrophils | The production of TNF-α and TGF-β by KCs is promoted by neutrophil-secreted IL-17; Express adhesion molecules to recruit neutrophils | Cholestatic liver injury, LPS-induced liver injury | (92, 93) | |
| NKT cells | KCs produce IL-1β to recruit and activate NKT cells | Alcoholic steatosis | (94) | |
| CD4+ T cells | KCs produce ROS, IL-6 and TNF-α to recruit CD4+ T cells. | Hepatic I/R injury | (95) | |
| T cells | KCs produce IL-10, TGF-β, ROS, IDO, PGE2/J2 to induce and maintain T cell tolerance or apoptosis | Liver transplantation, HBV infection, in vitro culture | (96–101) | |
| CD8+ T cells | KCs prime CD8+ T cells to differentiate into effector cells to kill viruses | HBV infection | ||
| Platelets | KCs promote adhesion of platelets on the KCs to encase the bacteria and facilitate anti-bacterial responses | Bacteria infection in the liver | ||
| MoMϕs | cholangiocytes | MoMϕs release IL-6 to promote the proliferation of cholangiocytes | Cholestatic liver disease | (102, 103) |
| cholangiocytes | MoMϕs are recruited by cholangiocytes-derived osteopontin and MCP-1 | Partial Hepatectomy | (104) | |
| LSECs | LSECs are activated by MoMϕs | Partial Hepatectomy | (105) | |
| NKT cells | MoMϕs promote NKT cells over-activation and cell death | NAFLD | (106) | |
| NKT cells | MoMϕs produce IL-12 to activate NKT cells, which inhibits liver regeneration | Partial hepatectomy | (107) |
KCs, Kuppfer cells; MoMϕs, Monocytes-derived macrophages; LSECs, liver sinusoidal endothelial cells; HSCs, hepatic stellate cells; NKT cells, natural killer T cell; IFN-γ, Interferon-gamma; CCL2, chemokine (C-C motif) ligand 2; TNF-α, tumor necrosis factor alpha; TGF-β, transforming growth factor beta; IL-17, interleukin 17; IL-1β, interleukin 1 beta; IL-6, interleukin 6; IL-10, interleukin 10; ROS, reactive oxygen species; IDO, indoleamine 2,3-dioxygenase; PGE2/J2, prostaglandin E2/J2; MCP-1, monocyte chemoattractant protein-1; ICC, intrahepatic cholangiocarcinoma; LPS, lipopolysaccharides; HBV, hepatitis B virus; I/R, ischemia/reperfusion.