CXCR3 and CCR5 Ligands in Rheumatoid Arthritis Synovium

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2001-01, Vol.98 (1), p.39-45
• Main Authors: Patel, Dhavalkumar D., Zachariah, Jason P., Whichard, Leona P.
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - metabolism; Biological and medical sciences; CCR5; CCR5 protein; chemokine; Chemokines - blood; CXCR3; CXCR3 protein; Diseases of the osteoarticular system; g-Interferon; Humans; Inflammatory joint diseases; IP-10; macrophage inflammatory protein 1^a; Medical sciences; Mig; Mip-1β; Receptors, CCR5 - analysis; Receptors, Chemokine - analysis; Receptors, CXCR3; rheumatoid arthritis; Synovial Membrane - chemistry; T-Lymphocytes - metabolism
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.2000.4957

The pathogenesis of rheumatoid arthritis (RA) may be mediated by Th1-type T cells. Since chemokine receptors CXCR3 and CCR5 are preferentially expressed on Th1 cells, we tested the expression and regulation of several chemokines, including those that signal through CXCR3 (interferon-γ-inducible protein of 10 kDa, IP-10, CXCL10; and monokine induced by interferon-γ, Mig, CXCL9) and CCR5 (macrophage inflammatory protein (Mip)-1α, CCL3; and Mip-1β, CCL4) in RA synovial fluids, synovial tissues, and blood. Synovial fluid (SF) protein levels of IP-10 (32.1 ± 10.5 ng/ml), Mig (15.0 ± 6.4 ng/ml), Mip-1β (0.7 ± 0.3 ng/ml), and Mip-1α (0.8 ± 0.1 ng/ml) were 100-, 50-, 25-, and 2-fold elevated in RASF compared to control SF (P < 0.001, P < 0.001, P < 0.001, and P < 0.02, respectively). Tissue levels of IP-10, Mig, and Mip-1β were significantly higher in RA than in OA (P < 0.01). Serum levels of IP-10 (3.1 ± 1.2 ng/ml) were higher in patients with seropositive RA compared to controls (1.2 ± 0.2 ng/ml) (P < 0.02). There was a gradient of IP-10, Mig, Mip-1α, and Mip-1β from the blood into the synovial fluid in RA. Infiltrating T cells around high endothelial venules in RA synovium and 90 ± 3% of SF CD3+CD4+ T cells expressed CXCR3, and 85 ± 2% of SF CD3+CD4+ T cells expressed CCR5. Chemokines, including IP-10, Mig, Mip-1α, and Mip-1β, may participate in the selective recruitment of CCR5+CXCR3+ T cells to the inflamed synovium.