| | Members | Sources | Ligand(s) | Target(s) | Major functions |
| | CXC | | | | | | CXCL1/groα | FLS, chondrocyte, macrophage, endothelial cell, synovial lining cell, and osteoclast | CXCR2, DARC | Neutrophil, macrophage, and fibroblasts | Enhances collagen deposition on RA fibroblasts, thereby fibrillating the synovium. | | CXCL4/PF4 | Macrophage, monocyte, and T cell | CXCR3 | Neutrophil, fibroblast, monocyte, and Th17 cell | Prevents monocyte apoptosis, induces differentiation of macrophages and enhances monocyte phagocytosis and oxygen radical production, exacerbates synovial inflammation, and promotes its chronicity by attracting and activating monocytes to the inflamed tissue. | | CXCL5/ENA-78 | Monocyte, fibroblast, synovial lining cell, macrophage, and endothelial cell | CXCR2, DARC | Neutrophil, Th17 cell, and FLS | Potent chemotactic factor for neutrophils and also an angiogenic factor. Increased levels of CXCL5 contribute to enhanced levels of RANKL expression. | | CXCL6/GCP-2 | Fibroblast, endothelial cell | CXCR2 | Neutrophil, vascular endothelial cell, and chondrocyte | Plays an important role in neutrophil migration and angiogenesis, promotes angiogenesis, and aggravates joint inflammation. | | CXCL7/CTAP-III | Macrophage, monocyte | CXCR2 | Neutrophil, connective tissue cell | It has an angiogenic effect that affects many aspects of connective tissue metabolism, including the proliferation of synovial fibroblasts and stimulation of synovial fibrosis. | | CXCL8/IL-8 | Synoviocyte, macrophage, synovial lining cell, endothelial cell, and monocyte | CXCR1, CXCR2, and DARC | Neutrophil, osteoblast, NK cell, T cell, synovial cell, and chondrocyte, macrophage | Regulates leukocyte adhesion molecule expression and acts as a mediator of angiogenesis. | | CXCL9/Mig | Synoviocyte, macrophage, neutrophil, monocyte, endothelial cell, fibroblast, and keratinocyte | CXCR3 | T cell, eosinophil, monocyte, and NK cell | Promotes recruitment of activated T lymphocytes and mast cell precursors and their migration to the site of inflammation. | | CXCL10/IP-10 | Synoviocyte, leukocyte, FLS, chondrocyte, neutrophil, monocyte, endothelial cell, fibroblast, and keratinocyte | CXCR3 | Macrophage, FLS, T cell, eosinophil, monocyte, and NK cell | Induces osteoclast differentiation and mediates RANKL expression in synovial CD4+ T cells. | | CXCL12/SDF-1 | Synoviocyte, endothelial cell, osteoblast, and stromal cell | CXCR4 | T cell, monocyte, endothelial cell, osteoclast, and stromal cell | Involved in the recruitment of CD4+ T cells to the RA synovium, synovial inflammation, and synovial lymphoid neogenesis. It binds to endoglin, which mediates the development of integrin-dependent leukocyte transendothelial migration, osteoclastogenesis, and bone erosion, leading to radiological progression of RA. | | CXCL13/BLC | Fibroblast, endothelial cell, follicular dendritic cell, CD4+ T cell, monocyte, and macrophage | CXCR5 | B cell, Tfh cell, Th17 cell, and Treg cell | Coordinates the migration and preferential sequestration of B and T cells in the inflammatory areas. | | CXCL16 | Macrophage, fibroblast, dendritic cell, monocyte, B cell, T cell, smooth muscle cell, and endothelial cell | CXCR6 | T cells, NK cell, B cell, FLS, plasma cell, and APC | Mediates leukocyte infiltration into synovial tissue involving the MAP kinase (MAPK) pathway and also in lymphocyte recruitment and lymph node organization. |
| | CC | | | | | | CCL2/MCP-1 | Synoviocyte, fibroblast, macrophage, and osteoblast | CCR2, CCR10, | Monocyte, T cell, NK cell, basophil, macrophage, and osteoclast | Induces angiogenesis, recruits macrophages to the joints, and involves in TNF-mediated osteoclast differentiation. | | CCL3/MIP-1α | Synoviocyte, monocyte, fibroblast, FLS, neutrophil, macrophage, lymphocyte, basophil, mast cell, and dendritic cell | CCR1, CCR5, and CCR3 | Monocyte, T cell, B cell, NK cell, basophil, eosinophil, and dendritic cell | Induces leukocyte chemotaxis, promotes the circulation of T cells into the inflammatory tissues, activates proinflammatory cytokines and RANKL by modulating activation of the PI3K/AKT signaling pathway, and upregulates CD4+ T cells. | | CCL5/RANTES | Fibroblast, T cell, endothelial cell, chondrocyte, monocyte, and macrophage | CCR1, CCR3, and CCR5 | Monocyte, T cell, NK cell, eosinophil, and basophil | Induces MMP-1 and MMP-13 expression as well as collagenase activity by activating RA synovial fibroblasts and may promote IL-1β-induced bone destruction. | | CCL13/MCP-4 | Chondrocyte, fibroblast, epithelial cell, and endothelial cell | CCR2, CCR3 | Eosinophil, monocyte, T cell, FLS, and basophil | Stimulates proliferation of synovial fibroblasts. | | CCL18/PARC | Neutrophil, dendritic cell | Unknown | T cell, APC, B cell, and macrophage | Promotes the recruitment of T cells by APC. | | CCL20/MIP-3α | Synovial lining cell, monocyte | CCR6 | Th17 cell, B cell, monocyte, dendritic cell, osteoblast, and osteoclast | Recruits IL-17-producing CCR6+ Th17 cells into the synovium and promotes osteoblast proliferation and osteoclast differentiation and may cooperate with the RANKL to affect bone formation and resorption. | | CCL25/TECK | Dendritic cell, epithelial cell, endothelial cell, and macrophage | CCR9 | Macrophage, monocyte, and T cell | CCL25 may be involved in the differentiation of monocytes into macrophages, especially in RA. |
| | C | | | | | | XCL1 | CD8+ T cell, CD4+ Th1 cell, and NK cell | XCR1 | Monocyte, FLS, T cell, thymocyte, B cell, NK cell, neutrophil, and CD8+ dendritic cell | Promotes T cell chemotaxis, stimulates the accumulation of T cells in arthritis joints, and downregulates production of MMP-2 by synovial fibroblasts. |
| | CX3C | | | | | | CX3CL1/Fractalkine | Monocyte, macrophage, FLS, endothelial cell, and dendritic cell | CX3CR1 | T cell, CD16+ monocyte, macrophage, FLS, and osteoclast | Mediates angiogenesis, enhances the adhesion of senescent T cells to synovial fibroblasts, costimulates the production of proinflammatory cytokines, and regulates cytoskeletal structure, proliferation, and migration of synovial fibroblasts. |
|
|
