Background Rheumatoid arthritis (RA) is characterized by accumulation of leukocytes in the synovial membrane and fluid of affected joints. Chemokine receptors on leukocytes mediate recruitment of these cells and identification of involved receptors offers potential for development of therapeutic interventions. Monocytes/macrophages play a key role in RA, contributing to inflammation, cartilage destruction and bone erosion. Monocytes migrate from the blood into the synovium where they differentiate into macrophages. Activated macrophages produce large quantities of inflammatory cytokines and chemokines including IL-1β, TNFα and CXCL8, and also proteases such as matrix metalloproteinase (MMP)-9 and MMP-12. The degree of macrophage infiltration correlates to the radiological progression of joint destruction.
Chemokine receptor CCR9 is expressed on monocytes/macrophages in peripheral blood and synovium and expression is up-regulated in RA. The differentiation of monocytes into macrophages within the synovium is suggested to involve CCR9 under both inflammatory and homeostatic conditions. Due to the greater numbers of monocytes/macrophages in rheumatoid compared to healthy synovium, CCR9 and its sole ligand CCL25 may, by stimulating differentiation of these cells, contribute to the pathogenesis of RA.
Objectives This study investigated the course of antigen-induced arthritis in CCR9 deficient C57BL/6 mice in comparison to wild type animals to determine whether CCR9 is critical for disease progression.
Methods Methylated bovine serum albumin was used for induction of uni-lateral arthritis by direct injection into the knee joint of a preimmunized animal. Arthritis is confined to the injected joint allowing comparison with the normal opposing joint. Clinical severity of arthritis was assessed by measuring swelling in the arthritic joint in comparison to the normal joint. Histological analysis was performed to assess the extent of leukocyte infiltration and cartilage depletion.
Results Levels of swelling were not significantly different between wild type and CCR9 deficient mice. Similarly there was no significant difference in histological severity of arthritis when comparing CCR9-deficient mice to wild type mice.
Conclusions CCR9 was not required for development of synovitis and cartilage destruction in the murine model of arthritis employed in this study. This may reflect a true lack of a pathogenic role of CCR9 on monocytes/macrophage function in vivo or it may reflect differences in the current antigen-induced arthritis model when compared to human RA.
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Disclosure of Interest None Declared