Table 1.
Key Roles of Chemokines and Chemokine Receptors in Health and Diseases
| Chemokine | Expression and Key Roles | Receptor |
|---|---|---|
| CCL1 | - Produced by activated monocytes, macrophages and T cells. - Induces cytokine secretion and the migration of immune cells. - Activates NK cells |
CCR8 |
| CCL2 | - Promotes the migration and trafficking of leukocytes, including monocytes, DCs, T cells and NK cells. | CCR2 ACKR1 ACKR2 |
| CCL3 | - Secreted by several hematopoietic and non-hematopoietic cells. - Induces inflammatory cells recruitment, wound healing, maintaining effector immune response and inhibition of stem cells. - Activates cells responsible for bone resorption and bone destruction. - Induces NK cell activities. |
CCR1 CCR5 ACKR2 |
| CCL4 | - Mainly secreted by macrophages. - Acts as chemoattractant for macrophages, monocytes, NK cells, immature DCs, and coronary endothelial cells. - Activates NK cells. |
CCR5 ACKR2 |
| CCL5 | - Expressed by T cells, macrophages, synovial fibroblasts, platelets, tubular epithelium, and certain tumor cells. - Triggers recruitment of leukocytes into inflammatory sites. - Stimulates the activation and proliferation of specific NK cells to produce CC chemokine-activated killer cells. - CCL5 produced by CD8+ T cells inhibits HIV entry into target cells. |
CCR1 CCR3 CCR5 ACKR2 |
| CCL6 | - Produced by macrophages, keratinocytes, fibroblasts, skeletal muscle, vascular smooth muscle cells. - Acts as chemotactic for macrophages, monocytes, and T cells. |
CCR1 |
| CCL7 | - Expressed by stromal cells, airway smooth muscle cells, and keratinocytes, and tumor cells. - Acts as a chemoattractant for leukocytes, including monocytes, basophils, eosinophils, basophils, NK cells, DCs, and activated T lymphocytes. |
CCR1 CCR2 CCR3 CCR5 CCR10 ACKR2 |
| CCL8 | - Induces leukocyte chemotaxis, HIV entry, and inflammation. - Highly expressed by tumor-associated macrophages, and its presence promotes tumor progression. |
CCR1 CCR2 CCR3 CCR5 ACKR2 |
| CCL9 | - Produced by macrophages and osteoclasts. - Functions as a cell survival factor. - Important for the recruitment of myeloid progenitors to intestinal tumors and enhancement of invasion. |
CCR1 |
| CCL11 | - Produced by endothelial cells, epithelial cells, eosinophils, fibroblasts, and keratinocytes. - Stimulates the migration of macrophages, Th2 cells, neutrophils, mast cells, basophils, eosinophils, and neural progenitor cells. - Highly expressed at sites of brain injury and is correlated with neurodegeneration and aging. |
CCR2 CCR3 CCR5 |
| CCL12 | - M1 marker as highly expressed by macrophages and is associated with monocyte-derived macrophage and fibroblast recruitment. - Inhibits wound healing. |
CCR2 |
| CCL13 | - Chemoattractant for eosinophils, basophils, monocytes, macrophages, immature DCs, and T cells - Acts on epithelial, muscular and endothelial cells by inducing immunomodulatory responses. |
CCR1 CCR2 CCR3 ACKR2 |
| CCL14 | - Acts on macrophages, monocytes, and THP-1 cells. - Involved in several diseases, including allergic airway inflammation and certain cancers. |
CCR1 CCR3 CCR5 ACKR2 |
| CCL15 | - Chemoattractant for immune cells such as monocytes and eosinophils - Expressed by lung leukocytes, alveolar macrophages, basophils, heart and skeletal muscles. |
CCR1 CCR3 |
| CCL16 | - Expressed by human plasma cells and liver cells. - Attracts lymphocytes, monocytes and DCs. - Activates angiogenesis in vascular endothelial cells and has myelosuppressive activities. |
CCR1 CCR2 CCR5 CCR8 |
| CCL17 | - Produced by peripheral blood mononuclear cells and specifically by a subset of CD11b+ DCs present in primary and secondary lymphoid organs. - Involved in the induction of many immune and inflammatory responses. - Activates NK cells. |
CCR4 ACKR2 |
| CCL18 | - Secreted primarily by myeloid cells, M2 macrophages, alveolar macrophages, tolerogenic DCs, and keratinocytes. - Highly expressed in skin lesions. - Induces trafficking of human peripheral blood Th2 cells and Treg cells. - Acts as an antagonist by binding to CCR1-5, leading to inhibition of cellular recruitment and chemotaxis. |
CCR8 |
| CCL19 | - Produced by mature DCs, stromal cells in the thymus and by T cell area of secondary lymphoid tissues. - Induces DC morphologic change and T cell thymic development. - Inhibits DC apoptosis. |
CCR7 ACKR4 CCRL2 |
| CCL20 | - Produced by psoriatic keratinocytes and endothelial cells. - Induces immune cells’ migration. - Crucial in mucosal immune surveillance. - Inducing the migration of DCs and T cells. |
CCR6 |
| CCL21 | - Expressed by endothelial venules in lymph nodes, and spleen. - Acts on mature DCs, B cells, and T cells. - Implicated in leukocyte infiltration into tissues such as the CNS. - Activates NK cells. |
CCR7 ACKR4 |
| CCL22 | - Produced by the thymus and myeloid cells, M2 macrophages, and monocyte-derived DCs. - Acts as a chemoattractant for NK cells, monocytes, DCs and antigen-experienced T lymphocytes. - Stimulates interactions between Treg cells and DCs in the lymph nodes. |
CCR4 ACKR2 |
| CCL23 | - Recruits resting T lymphocytes, DCs, and monocytes. - Inhibits proliferation of myeloid progenitor cells and promotes angiogenesis. - Acts as chemoattractant for osteoclast to promote bone formation. |
CCR1 |
| CCL24 | - Promotes immune cell trafficking and activation. - Involved in inflammation and fibrosis of the lung and skin. |
CCR3 |
| CCL25 | - Expressed by small intestinal epithelium. - Induces the recruitment of T and B cells. |
CCR9 ACKR4 |
| CCL26 | - Produced by eosinophils, basophils, DCs, smooth muscle cells, epithelial cells, fibroblasts and non-hematopoietic cells. - Has pro- and anti-inflammatory roles, by acting as CCR3 agonist and CCR1, CCR2 and CCR5 antagonist. |
CCR1 CCR2 CCR3 CCR5 |
| CCL27 | - Acts as chemoattractant for antigen-specific T lymphocytes. - Expressed in the brain and upregulated in atopic dermatitis. |
CCR10 |
| CCL28 | - Expressed by columnar epithelial cells in the gut, breast, salivary glands, and the lung. - Controls the mucosal homing of T and B lymphocytes expressing CCR10 and the migration of CCR10+ eosinophils. |
CCR3 CCR10 |
| CXCL1 | - Promotes angiogenesis and regulates recruitment of neutrophils and basophils during inflammation. - Important for Th17 cells’ differentiation. - Involved in regulating the NLRP3 inflammasome |
CXCR2 |
| CXCL2 | - Promotes inflammation, injury repair, the reorganization of the cytoskeleton, cell migration, adhesion and immune responses - Leads to recruitment and adhesion of neutrophils during inflammation. |
CXCR2 |
| CXCL3 | - Neutrophil chemoattractant. - Produced by tumor and stromal cells and related to tumor initiation, angiogenesis, and metastasis. - Facilitates adipogenic differentiation. |
CXCR2 |
| CXCL4 | - Induces monocyte chemotaxis and arrest. - Induces CCR1 endocytosis. - Important player in atherogenesis. |
CCR1 CXCR3 |
| CXCL5 | - Induces neutrophil trafficking as well as tumor migration and invasion. - Induces angiogenesis. |
CXCR2 |
| CXCL6 | - Expressed by macrophages, epithelial and mesenchymal cells during inflammation. - Exerts neutrophil-activating and angiogenic activities. - Has antibacterial effects. |
CXCR1 CXCR2 |
| CXCL7 | - Chemoattractant and activator of neutrophils. - Participates in a variety of cellular processes, such as DNA synthesis, glycolysis, and cAMP accumulation. - Acts as an antimicrobial protein. |
CXCR2 |
| CXCL8 | - Secreted by blood monocytes, alveolar macrophages, fibroblasts, endothelial cells, and epithelial cells. - Induces the recruitment of neutrophils and granulocytes, and promotion of angiogenesis. - Induces NK cells chemokinesis. |
CXCR1 CXCR2 |
| CXCL9 | - Chemoattractant for effector T cells, activated NK and Th1 cells into sites of inflammation. | CXCR3 |
| CXCL10 | - Produced by monocytes, neutrophils, endothelial cells, keratinocytes, DCs, and astrocytes. - Promotes leukocyte trafficking and homing to inflamed tissues, leading to tissue damage. - Recruits NK cells. |
CXCR3 |
| CXCL11 | - Regulated by IFN - Chemoattractant for IL-2 activated T cells. - Upon binding to CXCR7, it is associated with invasiveness of tumor cells. |
CXCR3 CXCR7 |
| CXCL12 | - Expressed by bone marrow stromal cells - Involved in homeostatic processes such as lymphopoiesis and embryogenesis. - Induces the recruitment of hematopoietic progenitor and stem cells. |
CXCR4 CXCR7 |
| CXCL13 | - Expressed by follicular DCs, T cells, and B cells. - Induces organizing and migration of B cell follicles. |
CXCR5 ACKR4 |
| CXCL14 | - Stimulates migration of B cells, NK cells, and monocytes. - Upregulated in several cancers. |
ACKR2 |
| CXCL15 | - Expressed in the lung as well as other mucosal and endocrine organs. - Induces neutrophils recruitment during inflammation. |
Not defined |
| CXCL16 | - Produced by macrophages and DCs. - Regulates immune cells chemotaxis, and induces endothelial cells proliferation, migration, and angiogenesis. |
CXCR6 |
| CXCL17 | - Myeloid cell-attracting chemokine. - Produced by the airways at normal and inflammatory conditions. |
Possibly GPR35 |
| CX3CL1 | - Expressed by immune and non-immune cells. - Induces migration and adhesion of macrophages, NK cells, and T cells. - Implicated in multiple inflammatory diseases. |
CX3CR1 |
| XCL1 | - Secreted by NK cells and T cells. - Induces chemotaxis of T cells, B cells, NK cells, and neutrophils. - When produced by tumor cells, it induces PD1/PD-L1 interaction and the inhibition of CD8+ T cells in tumor microenvironment. |
XCR1 |
| XCL2 | - Expressed by NK and T cells and induces their chemotaxis. - Increased expression correlates with cancer progression. |
XCR1 |
Notes: Chemokines are divided into four main sub-families which are CC, CXC, CX3C, and XC, depending on the position of the cysteine residues in their amino acid sequences. They play important roles in the inflammatory and homeostasis processes of the body. Chemokine ligands signal mainly through G-protein coupled receptors which are considered the “conventional” receptors. These receptors are named according to the chemokine ligands they interact with. On the other hand, there are five “atypical” chemokine receptors (ACKRs) which are DARC, D6, CXCR7, CCRL1, and CCRL2, also known as ACKR1-5 respectively. These atypical chemokine receptors have similar structures to the conventional chemokine receptors, and their primary role is scavenging or sequestering the chemokine ligands, thus controlling the signaling response through the conventional chemokine receptors and regulating the immune responses.
Abbreviations: ACKR, atypical chemokine receptor; DC, dendritic cell; GPR35, G protein-coupled receptor 35; HIV, human immunodeficiency virus; IL-2, interleukin 2; NK, natural killer cell; PD, programmed death; PD-L, programmed death ligand; Th, T helper cell; Treg, T regulatory cell.