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Open Access Research article

Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5

Caroline Schmutz1*, Alison Hulme1, Angela Burman2, Mike Salmon2, Brian Ashton13, Christopher Buckley2 and Jim Middleton13

Author Affiliations

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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Arthritis Res Ther 2005, 7:R217-R229  doi:10.1186/ar1475

Published: 16 December 2004

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.

Keywords:
chemokine receptors; CXCR5; microarrays; rheumatoid synovium