From: Targeting the Chemokine System in Rheumatoid Arthritis and Vasculitis
| Chemokine | Other names | Receptor |
|---|---|---|
| CXCL1 | GROα, MGSA, mouse KC | CXCR2, ACKR1 |
| CXCL2 | GROβ, MIP-2α, mouse MIP2 | CXCR2, ACKR1 |
| CXCL3 | GROγ, MIP-2β | CXCR2, ACKR1 |
| CXCL4 | PF4 | Unknown |
| CXCL4L1 | PF4V1 | Unknown |
| CXCL5 | ENA-78, mouse LIXa | CXCR2, ACKR1 |
| CXCL6 | GCP-2 (human only) | CXCR1, CXCR2, ACKR1 |
| CXCL7 | NAP-2 | CXCR2, ACKR1 |
| CXCL8 | IL-8 (human only) | CXCR1, CXCR2, ACKR1 |
| CXCL9 | Mig | CXCR3 |
| CXCL10 | IP-10 | CXCR3 |
| CXCL11 | I-TAC | CXCR3, ACKR1, ACKR3 |
| CXCL12 | SDF-1 | CXCR4, ACKR3 |
| CXCL13 | BLC, BCA-1 | CXCR5, ACKR1, ACKR4 |
| CXCL14 | BRAK | Unknown |
| CXCL15 | Lungkine (mouse only) | Unknown |
| CXCL16 | CXCR6 | |
| CCL1 | I-309, mouse TCA3 | CCR8 |
| CCL2 | MCP-1, mouse JE | CCR2, ACKR1, ACKR2 |
| CCL3b | MIP-1α, LD78α | CCR1, CCR5, ACKR2 |
| CCL3L1 | LD78β | CCR1, CCR3, CCR5, ACKR2 |
| CCL4 | MIP-1β | CCR5, ACKR2 |
| CCL4L1 | LAG-1 | CCR5 |
| CCL5 | RANTES | CCR1, CCR3, CCR5, ACKR2 |
| CCL6 | C-10, MRP-1 (mouse only) | Unknown |
| CCL7 | MCP-3, mouse Fic or MARC | CCR2, CCR3, ACKR1, ACKR2 |
| CCL8 | MCP-2 | Human: CCR1, CCR2, CCR3, CCR5, ACKR1, ACKR2; mouse: CCR8, ACKR1, ACKR2 |
| CCL9/10 | MIP-1γ, MRP-2 (mouse only) | Unknown |
| CCL11 | Eotaxin-1 | CCR3, ACKR2 |
| CCL12 | MCP-5 (mouse only) | CCR2 |
| CCL13 | MCP-4 (human only) | CCR2, CCR3, CCR5, ACKR1, ACKR2 |
| CCL14 | HCC-1 (human only) | CCR1, ACKR1, ACKR2 |
| CCL15 | Leukotactin-1, HCC-2, MIP-5 (human only) | CCR1, CCR3 |
| CCL16 | HCC-4, NCC-4, LEC (human only) | CCR1, CCR2, CCR5, ACKR1 |
| CCL17 | TARC | CCR4, ACKR1, ACKR2 |
| CCL18 | PARC, DC-CK1 (human only) | CCR8 |
| CCL19 | MIP-3β, ELC | CCR7, ACKR4 |
| CCL20 | MIP-3α, LARC | CCR6 |
| CCL21 | SLC, 6CKine | CCR6, CCR7, ACKR4 |
| CCL22 | MDC | CCR4, ACKR1, ACKR2 |
| CCL23 | MPIF-1, MMP-3 (human only) | Unknown |
| CCL24 | Eotaxin-2, MPIF-2 | CCR3 |
| CCL25 | TECK | CCR9, ACKR4 |
| CCL26 | Eotaxin-3 | CCR3, CX3CR1 |
| CCL27 | CTAK | CCR10 |
| CCL28 | MEC | CCR3, CCR10 |
| XCL1 | Lymphotactin α, SCM-1α | XCR1 |
| XCL2 | Lymphotactin β, SCM-1β | XCR1 |
| CX3CL1 | Fractalkine | CX3CR1 |
From: Targeting the Chemokine System in Rheumatoid Arthritis and Vasculitis
| Receptor | Cell expression | General immune function |
|---|---|---|
| Classical chemokine receptors | ||
| CXCR1 | Neutrophils and lower expression on monocytes, NK cells, mast cells, basophils, CD8+ TEFF cells and endothelial cells | Neutrophil trafficking |
| CXCR2 | Neutrophils and lower expression on monocytes, NK cells, mast cells, basophils, CD8+ T cells and endothelial cells | B cell lymphopoiesis, neutrophil egress from bone marrow and neutrophil trafficking |
| CXCR3 | TH1 cells, CD8+TCM cells and TEM cells, NK cells, NKT cells, plasmacytoid dendritic cells, B cells, Treg cells and TFH cells | Type 1 adaptive immunity |
| CXCR4 | Most leukocytes and endothelial cells | Hematopoiesis, organogenesis and bone marrow homing |
| CXCR5 | B cells, TFH cells, TFR cells CD8+ TEM cells | B cell and T cell trafficking in lymphoid tissue to the B cell zone or follicles |
| CXCR6 | TH1 cells, TH17 cells, γδT cells, ILCs, NKT cells, NK cells, plasma cells, endothelial cells | ILC function and adaptive immunity |
| CCR1 | Monocytes, macrophages, neutrophils, TH1 cells, basophils, dendritic cells | Innate immunity and adaptive immunity |
| CCR2 | Monocytes, macrophages, TH1 cells, immature dendritic cells, basophils, NK cells and endothelial cells | Monocyte trafficking and type 1 adaptive immunity |
| CCR3 | Eosinophils and lower expression on basophils and mast cells | Type 2 adaptive immunity, eosinophil distribution and trafficking |
| CCR4 | TH2 cells, skin-homing T cells and lung-homing T cells, Treg cells and lower expression on TH17 cells, CD8+T cells, monocytes, B cells and immature dendritic cells | Homing of T cells to the skin and lungs and type 2 immune responses |
| CCR5 | Monocytes, macrophages, TH1 cells, NK cells, Treg cells, CD8+ T cells, dendritic cells and neutrophils | Type 1 adaptive immunity |
| CCR6 | TH17 cells, immature dendritic cells, γδT cells, NKT cells, NK cells, Treg cells and TFH cells | Immature dendritic cell trafficking, GALT development and type 17 adaptive immune responses |
| CCR7 | Naïve T cells, TCM cells, TRCM cells, mature dendritic, B cells | Mature dendritic cell, B cell and T cell trafficking in lymphoid tissue to T cell zone and egress of dendritic cells and T cells from tissue |
| CCR8 | TH2 cells, Treg cells, skin TRM cells, γδT cells, monocytes and macrophage | Immune surveillance in skin, type 2 adaptive immunity and thymopoiesis |
| CCR9 | Gut-homing T cells, thymocytes, B cells, dendritic cells and plasmacytoid dendritic cells | Homing of T cells to the gut, GALT development and function and thymopoiesis |
| CCR10 | Skin-homing T cells and IgA-plasmablasts | Homing immunity at mucosal sites and immune surveillance in the skin |
| XCR1 | Cross-presenting CD8+ dendritic cells and thymic dendritic cells | Antigen cross-presentation by CD8+ dendritic cells |
| CX3CR1 | Resident monocytes, macrophages, microglia, TH1 cells, CD8+ TEM cells, NK cells, γδT cells and dendritic cells | Patrolling monocytes in innate immunity, microglial cell and NK cell migration and type 1 adaptive immunity |
| Atypical chemokine receptors | ||
| ACKR1 (DARC) | Red blood cells and endothelial cells | Chemokine transcytosis and chemokine scavenging |
| ACKR2 (D6) | Dendritic cells, B cells and lymphatic endothelium | Chemokine scavenging |
| ACKR3 (CXCR7) | B cell and stromal cells | Shaping chemokine gradients for CXCR4 |
| ACKR4 (CCRL1; CCX-CKR) | Thymic epithelium | Chemokine scavenging |
From: Targeting the Chemokine System in Rheumatoid Arthritis and Vasculitis
| Target | Drug (Type of drug) | Type of study | Efficacy | Study outcome |
|---|---|---|---|---|
| CXCL10 | MDX-1100 (antibody) | Phase II | Mildly effective | The ACR20 response at week 12 was 54% (MDX1100 and MTX) and 17% (placebo and MTX) |
| CCL2 | ABN912 (antibody) | Phase Ib | Not effective | ABN912 did not result in any clinical improvement. |
| CCR1 | CP-481,715 (small molecules) | Phase Ib | Mildly effective | CP-481,715 reduced tender and swollen joint count, and macrophages infiltration into the synovial tissue than those of placebo. |
| CCX354-C (small molecules) | Phase II | Mildly effective | The ACR20 response at week 12 was 39% (placebo), 43% (CCX354-C; 100mg twice daily) and 52% (CCX354-C; 200 mg once daily) | |
| MLN3897 (small molecules) | Phase IIa | Not effective | The ACR20 response at week 12 was 35% (MLN3897) and 33% (placebo). | |
| CCR2 | MLN1202 (antibody) | Phase IIa | Not effective | Patients treated with CCR2 monoclonal antibody or placebo for 6 weeks. No clinical improvement |
| CCR5 | SCH351125 (small molecules) | Phase Ib | Not effective | The ACR20 response at week 4 was 20% (SCH351125) and 33% (placebo). |
| AZD5672 (small molecules) | Phase IIb | Not effective | The ACR20 response at week 12 was around 35% (AZD5672) and 38% (placebo). | |
| UK-427,857 (small molecules) | Phase IIa | Not effective | The ACR20 response at week 12 was 23.7% (UK-427,857) and 23.8% (placebo). | |
| CX3CL1 | E6011 (antibody) | Phase I/II | Effective? (no placebo) | ~60% treated patients had at ACR20 response at week 12. |
