Table 2.
Tissue distribution, biological functions, and ligand specificity of atypical receptors for chemokines (ACKRs).
| Receptor | Characteristics | |
|---|---|---|
|
ACKR1
(Duffy Antigen for Chemokines, DARC) |
Ligands | Pro-inflammatory chemokines: CXCL1, CXCL5, CXCL6, CXCL8, CXCL11, CCL2, CCL5, CCL7, CCL13 [246] Chemokines with mixed function: CCL17 [246] Homeostatic chemokines: CCL14 [246] Non-chemokine ligands: co-receptor for Plasmodium vivax [246] and Plasmodium knowlesi [262] |
| Tissue/cell expression | Endothelium of small veins and postcapillary venules [249], erythrocytes [251], Purkinje cells in cerebellum [263] | |
| Function | Chemokine transporter [264] Chemokine depot [265] |
|
|
Importance
in glioma |
Increased expression in astrocytoma tissues [269] mRNA for ACKR1 detected in various astrocytoma grades [269] Promotion of tumoral angiogenesis by binding CXCL8 [269] |
|
| ACKR2 (D6) | Ligands | Pro-inflammatory chemokines: CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL12, CCL13 [104] Chemokines with mixed function: CCL17, CCL22 [104] Homeostatic chemokines: CCL14 [104] Non-chemokine ligands: co-receptor for HIV-1 and HIV-2 [270] |
| Tissue/cell expression | Lymphatic endothelium of gut, lung, and skin [271], placental trophoblast [272], hematopoietic stem cells [249], leukocytes: innate B cells [245], macrophages, dendritic cells, tissue mast cells [273] | |
| Function | Chemokine scavenger [275] Anti-inflammatory activity [276,277] |
|
|
Importance
in glioma |
Not described yet | |
| ACKR3 (CXCR7) | Ligands | Homeostatic chemokines: CXCL11 [281], CXCL12 [282] Non-chemokine ligands: Adrenomedullin, MIF, BAM22 [104] Viral chemokine: vCCL2/vMIP-II [283] |
| Tissue/cell expression | Smooth muscle cells of venules and arterioles [289], leukocytes: T lymphocytes, B lymphocytes, dendritic cells [289], epithelium [287] | |
| Function | Chemokine scavenger [286] Modulator of CXCR4 receptor [288] |
|
|
Importance
in glioma |
High expression in glioma tumor cells [307], microglia, and tumor-associated vascular endothelium [308] Expression in glioma related to the survival prognosis [310] Autocrine regulator of meningioma development and vascularization [312] |
|
|
ACKR4 (CCRL1/CCXCKR) |
Ligands | Pro-inflammatory chemokines: CCL2, CCL8, CCL13, CCL19 [314] Chemokines with mixed function: CCL21 [314,316] Homeostatic chemokines: CCL25 [313,314], CXCL13 [313] |
|
Tissue/cell
expression |
Leukocytes, dendritic cells, T cells [313], lymph nodes, spleen, thymus [317] Non-lymphoid tissues: heart, kidney, placenta, trachea, and brain [313] Epithelium, bronchial cells, keratinocytes [317] |
|
| Function | Chemokine scavenger [315,316,317] Modulator of CXCR3 receptor by forming complexes [318] |
|
|
Importance
in glioma |
Not described yet | |
| ACKR5 * (CCRL2) | Ligands | Pro-inflammatory: CCL19 [330], CCL2, CCL5, CCL7, and CCL8 [329,331,332] Non-chemokine ligands: Chemerin [333] |
|
Tissue/cell
expression |
Leukocytes: neutrophils, monocytes, macrophages, basophils, mast cells, PMNs, CD4+ T cells, CD8+ T cells, pro- and pre-B cells, dendritic cells, NK cells, CD34+progenitor cells, epithelium, endothelium [327,328] | |
| Function | Chemokine presenter [328,333,336,337]. Regulation of other receptor functions by forming heterodimers [335]. |
|
|
Importance
in glioma |
Elevated expression in human glioma samples and cell lines [340] Upregulated CCRL2 in glioma promotes cell migration and invasion [340] |
|
|
ACKR6 * (PITPNM3) |
Ligands | Pro-inflammatory: CCL18 [346] |
|
Tissue/cell
expression |
Retina, brain, spleen, ovaries [346,347,348], tumor-associated macrophages [114,352] | |
| Function | Activator of intracellular calcium signaling [348,350] | |
|
Importance
in glioma |
Not described yet | |
*-not confirmed as atypical receptor yet, tentatively included in the ACKR family.