Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5 |
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Authors: | Email author" target="_blank">Caroline?SchmutzEmail author Alison?Hulme Angela?Burman Mike?Salmon Brian?Ashton Christopher?Buckley Jim?Middleton |
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Institution: | (1) Leopold Muller Arthritis Research Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK;(2) Division of Immunity and Infection, Medical Research Council Centre for Immune Regulation, University of Birmingham, Edgbaston, UK;(3) Institute for Science and Technology in Medicine, Medical School, Keele University, Stoke-on-Trent, UK |
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Abstract: | In patients with rheumatoid arthritis (RA), chemokine and chemokine receptor interactions play a central role in the recruitment
of leukocytes into inflamed joints. This study was undertaken to characterize the expression of chemokine receptors in the
synovial tissue of RA and non-RA patients. RA synovia (n = 8) were obtained from knee joint replacement operations and control non-RA synovia (n = 9) were obtained from arthroscopic knee biopsies sampled from patients with recent meniscal or articular cartilage damage
or degeneration. The mRNA expression of chemokine receptors and their ligands was determined using gene microarrays and PCR.
The protein expression of these genes was demonstrated by single-label and double-label immunohistochemistry. Microarray analysis
showed the mRNA for CXCR5 to be more abundant in RA than non-RA synovial tissue, and of the chemokine receptors studied CXCR5 showed the greatest upregulation.
PCR experiments confirmed the differential expression of CXCR5. By immunohistochemistry we were able to detect CXCR5 in all RA and non-RA samples. In the RA samples the presence of CXCR5
was observed on B cells and T cells in the infiltrates but also on macrophages and endothelial cells. In the non-RA samples
the presence of CXCR5 was limited to macrophages and endothelial cells. CXCR5 expression in synovial fluid macrophages and peripheral blood monocytes from RA patients was confirmed by PCR. The present
study shows that CXCR5 is upregulated in RA synovial tissue and is expressed in a variety of cell types. This receptor may
be involved in the recruitment and positioning of B cells, T cells and monocytes/macrophages in the RA synovium. More importantly,
the increased level of CXCR5, a homeostatic chemokine receptor, in the RA synovium suggests that non-inflammatory receptor–ligand
pairs might play an important role in the pathogenesis of RA. |
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