Table 2.
Chemokines involved in the pathogenesis of liver disease.
| Chemokine | Location in the liver | Function | Receptors and their distribution |
|---|---|---|---|
| CXC subfamily | |||
| CXCL1 | Hepatocytes, Kupffer cells, activated stellate cells; and endothelial cells [33, 34] | Neutrophil migration, innate immunity, acute inflammation, and angiogenesis | CXCR1: PMN, monocytes, and mast cells CXCR2: PMN, monocytes, and mast cells |
| CXCL2 | Hepatocytes, Kupffer cells, activated stellate cells; and endothelial cells [34, 35] | Neutrophil migration, innate immunity, acute inflammation, and angiogenesis | CXCR2: PMN, monocytes, and mast cells |
| CXCL3 | Hepatocytes, Kupffer cells, activated stellate cells, and endothelial cells [33, 34] | Neutrophil migration, innate immunity, acute inflammation, and angiogenesis | CXCR2: PMN, monocytes, and mast cells |
| CXCL4 | Sinusoidal endothelium, platelets, NK cells, T cells, and neutrophils [36] |
Chemotactic for neutrophils, monocytes, and fibroblasts |
CXCR3: memory T cells, Th1, Th2, Th17, and Treg, NKT |
| CXCL4L1 | Thrombin-stimulated platelets [37] | Angiogenesis and antitumoral chemokine |
CXCR3: memory T cells, Th1, Th2, Th17, Treg, and NKT |
| CXCL5 | Hepatocytes, Kupffer cells, and endothelial cells [33] | Neutrophil migration, innate immunity, acute inflammation, and angiogenesis | CXCR2: PMN, monocytes, and mast cells |
| CXCL6 | Microvascular endothelial cells [38] | Neutrophil migration and innate immunity |
CXCR1: PMN, monocytes, and mast cells CXCR2: PMN, monocytes, and mast cells |
| CXCL7 | Platelets [39] | Angiogenesis, innate immunity, neutrophil migration, and regenerating vascular integrity after injury |
CXCR1: PMN, monocytes, and mast cells CXCR2: PMN, monocytes, and mast cells |
| CXCL8 | Endothelial cells, Kupffer cells, biliary epithelial cells, and stellate cells [34] | Innate immunity, neutrophil migration, and angiogenesis |
CXCR1: PMN, monocytes, and mast cells CXCR2: PMN, monocytes, and mast cells |
| CXCL9 | Sinusoidal epithelial cells [40] | Th1, Th2, Th17, and Treg recruitment and adaptive immunity |
CXCR3: memory T cells, Th1, Th2, Th17, Treg, and NKT CCR3: eosinophils and basophils |
| CXCL10 | Hepatocytes and liver sinusoids [15] | Th1, Th2, Th17, and Treg recruitment and adaptive immunity |
CXCR3: memory T cells, Th1, Th2, Th17, Treg, and NKT CCR3: eosinophils and basophils |
| CXCL11 | Liver sinusoids [15] | Th1, Th2, Th17, and Treg recruitment and adaptive immunity |
CXCR3: memory T cells, Th1, Th2, Th17, Treg, and NK CCR3: eosinophils and basophils CCR5: monocytes, Th1 cells, and NK |
| CXCL12 | Biliary epithelium [15] | Stem cell migration and B-cell lymphopoiesis | CXCR4: T and B cells, monocytes, stem cells, and NKT |
| CXCL13 | Lymphocytes within microenvironments [41] | B-cell homing in lymphoid organ and liver and T-cell homing in the liver |
CXCR5: B cells CXCR3: memory T cells, Th1, Th2, Th17, Treg and NKT |
| CXCL14 | Macrophage and neutrophil [42] | Recruitment of monocytes/macrophages to the liver | Unknown |
| CXCL16 | Liver sinusoids biliary epithelium [15] | T-cell migration, recruitment of CD4+ T cells, and CD8+ T cells and B cells into the liver | CXCR6: memory T cells, Th1, NK and NKT |
| CXCL17 | Endothelial cells and hepatocellular carcinoma (HCC) cells [43] | Chemoattract DC and monocytes, angiogenesis, and carcinogenesis | Unknown |
|
| |||
| CC subfamily | |||
| CCL1 | Hepatocytes, hepatic stellate cells, endothelium, and Kupffer cells [44] | T-cell trafficking and Th2 response | CCR8: monocytes, Th2, Treg and NK |
| CCL2 | Hepatocytes, Kupffer cells, and stellate cells [44] | Th1 inflammation, T-cell and monocyte migration, and innate and adaptive immunity | CCR2: monocytes, memory T cells, basophils and pDC |
| CCL3 | Portal vessels, biliary epithelium, and sinusoidal endothelium [45, 46] | T-cell and monocyte migration, innate and adaptive immunity, inflammation,Th1 response, HIV infection, and hypersensitivity |
CCR1: monocytes, memory T cells, Th1 and NK CCR5: monocytes, Th1 cells and NK |
| CCL4 | Portal vessels, biliary epithelium, and sinusoidal endothelium [15] | Th1 response, adaptive immunity, inflammation, HIV infection | CCR5: monocytes, Th1 cells and NK |
| CCL5 | Portal vessels, platelets, T-cells, macrophages, liver-derived dendritic cells, and Kupffer cells [15] | T cell and monocyte migration, innate and adaptive immunity, inflammation, Th1 response, and HIV infection, and hypersensitivity |
CCR1: monocytes, memory T cells, Th1 and NK CCR3: eosinophils and basophils CCR5: monocytes, Th1 cells and NK |
| CCL7 | Portal vessels, monocytes, endothelial cells, smooth muscle cells, and human CD34 cells [47] | T-cell, NK cells, dendritic cells, basophils, eosinophils, and monocyte migration, innate and adaptive immunity, Th1 inflammation, and hypersensitivity |
CCR1: monocytes, memory T cells, Th1, and NK CCR2: monocytes, memory T cells, basophils and pDC CCR3: eosinophils and basophils CCR5: monocytes, Th1 cells, and NK |
| CCL8 | Portal and vascular endothelium [47] |
T-cell and monocyte migration, innate and adaptive immunity, Th1 inflammation, hypersensitivity, and HIV infection |
CCR1: monocytes, memory T cells, Th1, and NK CCR2: monocytes, memory T cells, basophils, and pDC CCR3: eosinophils and basophils CCR5: monocytes, Th1 cells, and NK |
| CCL11 | Foetal liver [48] | Eosinophil and basophil migration, allergic inflammation, and Th2 response |
CCR2: monocytes, memory T cells, basophils, and pDC CCR3: eosinophils and basophils CCR5: monocytes, Th1 cells, and NK CXCR3: memory T cells, Th1, Th2, Th17, Treg, and NKT |
| CCL12 | Kupffer cells [49] | Monocytes, T-cell and eosinophils migration, and allergic inflammation | CCR2: monocytes, memory T cells, basophils, and DC |
| CCL13 | Epithelial and endothelial cells [50] | T-cell and monocyte migration, innate and adaptive immunity, and Th1 inflammation |
CCR1: monocytes, memory T cells, Th1, and NK CCR2: monocytes, memory T cells, basophils, and pDC CCR3: eosinophils and basophils |
| CCL14 | Widely in liver and plasma [14] | T-cell and monocyte migration, hypersensitivity, innate and adaptive immunity, and inflammation |
CCR1: monocytes, memory T cells, Th1, and NK CCR3: eosinophils and basophils CCR5: monocytes, Th1 cells, and NK |
| CCL15 | Widely in liver [51] | T-cell, eosinophil, basophil, and monocyte migration, Th2 response, hypersensitivity, innate and adaptive immunity, and allergic inflammation |
CCR1: monocytes, memory T cells, Th1, and NK CCR3: eosinophils and basophils |
| CCL16 | Hepatocytes and biliary epithelial cells [52] | T-cell, eosinophil, basophil, and monocyte migration,Th2 response, hypersensitivity, innate and adaptive immunity, and allergic inflammation |
CCR1: monocytes, memory T cells, Th1, and NK CCR3: eosinophils and basophils |
| CCL17 | Keratinocytes, fibroblasts, stimulated monocytes, and certain DC [53] |
T-cell and monocyte migration, allergic inflammation, and Treg retention | CCR4: Th2 cells, Treg eosinophils, basophils, DC, and Treg |
| CCL18 | Portal area of livers with hepatitis C but not in normal livers [54] | Lymphocytes and immature DC activation | CCR3: eosinophils and basophils |
| CCL19 | Portal-associated lymphoid tissue [15] |
T-cell and DC homing to secondary lymphoid tissue and lymphoid development | CCR7: naive T, B, mature mDC, Th1, Th2, and Treg |
| CCL20 | Endothelial cells, macrophages, and DC in the livers [55] |
DC migration, memory T-cells, and Th17 cells at site of inflammation | CCR6: memory T cells, B cells, Th17, and immature mDC |
| CCL21 | Portal-associated lymphoid tissue [15] |
T-cell and DC homing to secondary lymphoid tissue; lymphoid development; T-cell recruitment; adaptive immunity; and Th1, Th2, Th17, and Treg inflammation |
CXCR3 (mouse): memory T cells, Th1, Th2, Th17, Treg, and NKT CCR7: naive T, B, mature mDC, Th1, Th2, and Treg |
| CCL22 | DC, B cell, and macrophages (Kupffer cells) [56] | T-cell and monocyte migration, allergic inflammation, Treg retention, and T-cell skin homing | CCR4: Th2 cells, Treg eosinophils, basophils, DC, and Treg |
| CCL23 | Macrophages (Kupffer cells) [57] | Chemotactic activity on resting T cell, monocytes, and neutrophils | CCR1: monocytes, memory T cells, Th1, and NK |
| CCL24 | Lower levels in the liver [58] | Eosinophil and basophil migration, allergic inflammation, and Th2 response | CCR3: eosinophils and basophils |
| CCL25 | macrophages, Kupffer cells, DC, and cholangiocytes [59] | Recruitment of adaptive immune cells to the liver. T-cell homing to gut and thymus and tolerogenic DC | CCR9: DC, memory T cells, and thymocytes |
| CCL26 | Vascular endothelial cells [60] | Eosinophil and basophil migration, allergic inflammation, and Th2 response | CCR3: eosinophils and basophils |
| CCL27 | No expression in liver and predominantly in the skin keratinocytes [61] | T-cell trafficking in the skin | CCR10: memory T cells and Treg |
| CCL28 | Biliary epithelium (cholangiocytes) [15] | T-cell homing to skin and bowel | CCR10: memory T cells and Treg |
|
| |||
| C subfamily | |||
| XCL1 | Not expressed in human liver [62] | NK-cell recruitment | XCR1: NK |
| XCL2 | Preferentially in CD8+ T cells [63] | NK-cell recruitment | XCR1: NK |
|
| |||
| CX3C subfamily | |||
| CX3CL1 | Biliary epithelium [64] | Th1 inflammation, T-cell, NK cell trafficking and adhesion, and innate and adaptive immunity | CX3CR1: monocytes, and Th1, NK |
CXCL: C-X-C motif chemokine ligand; CXCR: C-X-C motif chemokine receptor; CCL: C-C motif chemokine ligand; CCR: C-C motif chemokine receptor; XCL: X-C motif chemokine ligand; XCR: X-C motif chemokine receptor; CX3CL: C-X3-C motif chemokine ligand; CX3CR: C-X3-C motif chemokine receptor; Th1: T helper 1; Th2: T helper 2; Th17: T helper 17; Treg: regulatory T cell; NK: natural killer; NKT: natural killer T; DC: dendritic cell; pDC: plasmacytoid dendritic cell; mDC: myeloid dendritic cell; PMN: polymorphs.