Suppression of murine collagen-induced arthritis by vaccination of synovial vascular endothelial cells

Aims: Endothelial cells (ECs) lining the lumina of blood vessels are involved in leukocyte extravasation underlying inflammatory states, such as rheumatoid arthritis (RA). The rheumatoid pannus, the site of inflammation and joint destruction in the rheumatoid synovium, relies on the development of neovascular vessels to sustain its growth. We studied a method to selectively target and destroy new synovial blood vessels by vaccination with synovial EC. Main methods: Collagen-induced arthritis (CIA) mice were vaccinated with tumor necrosis factor (TNF)-alpha- stimulated EC (TNF-EC) antigen with an incomplete adjuvant. TNF-EC was used as a model of EC in synovial tissue on RA. Key findings: Arthritis was significantly decreased in TNF-EC vaccinated mice compared with non-vaccinated mice based on the arthritis score. Moreover, the TNF-EC vaccine suppressed bone erosion, hyperplasia of the synovium and expression of neovascular vessel as shown by hematoxylin-eosin staining, X-ray analysis and immunohistochemical. Significance: Vaccine therapy against vascular EC in synovial tissue may provide a novel approach to the treatment of RA. (C) 2013 Elsevier Inc. All rights reserved.