Open Access Highly Accessed Research article

Expression and function of junctional adhesion molecule-C in human and experimental arthritis

Gaby Palmer1, Nathalie Busso2, Michel Aurrand-Lions3, Dominique Talabot-Ayer1, Véronique Chobaz-Péclat2, Claudia Zimmerli3, Philippe Hammel3, Beat A Imhof3 and Cem Gabay1*

Author Affiliations

1 Division of Rheumatology, Department of Internal Medicine, University Hospital, 26 avenue Beau-Séjour, 1211 Geneva 14, Switzerland and Department of Pathology and Immunology, University of Geneva School of Medicine, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland

2 Division of Rheumatology, Department of Medicine, University Hospital, Nestlé 05-5029, 1011 Lausanne, Switzerland

3 Department of Pathology and Immunology, University of Geneva School of Medicine, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland

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Arthritis Research & Therapy 2007, 9:R65  doi:10.1186/ar2223

Published: 5 July 2007

Abstract

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule involved in transendothelial migration of leukocytes. In this study, we examined JAM-C expression in the synovium and investigated the role of this molecule in two experimental mouse models of arthritis. JAM-C expression was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of a monoclonal anti-JAM-C antibody were assessed in antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis. JAM-C was expressed by synovial fibroblasts in the lining layer and associated with vessels in the sublining layer in human and mouse arthritic synovial tissue. In human tissue, JAM-C expression was increased in rheumatoid arthritis (RA) as compared to osteoarthritis synovial samples (12.7 ± 1.3 arbitrary units in RA versus 3.3 ± 1.1 in OA; p < 0.05). Treatment of mice with a monoclonal anti-JAM-C antibody decreased the severity of AIA. Neutrophil infiltration into inflamed joints was selectively reduced as compared to T-lymphocyte and macrophage infiltration (0.8 ± 0.3 arbitrary units in anti-JAM-C-treated versus 2.3 ± 0.6 in isotype-matched control antibody-treated mice; p < 0.05). Circulating levels of the acute-phase protein serum amyloid A as well as antigen-specific and concanavalin A-induced spleen T-cell responses were significantly decreased in anti-JAM-C antibody-treated mice. In the serum transfer-induced arthritis model, treatment with the anti-JAM-C antibody delayed the onset of arthritis. JAM-C is highly expressed by synovial fibroblasts in RA. Treatment of mice with an anti-JAM-C antibody significantly reduced the severity of AIA and delayed the onset of serum transfer-induced arthritis, suggesting a role for JAM-C in the pathogenesis of arthritis.