The synovium as a privileged site in rheumatoid arthritis: Cadherin-11 as a dominant player in synovial pathology

Abstract

Rheumatoid arthritis is a systemic disease in which an autoimmune response translates primarily into joint inflammation with attendant joint destruction. While evidence implicates both the adaptive and innate immune system in rheumatoid synovitis, several lines of evidence now support the concept that the synovial tissue itself actively participates in the destructive inflammatory processes of arthritis. Specifically, the resident mesenchymal cells, the fibroblast-like synoviocytes (FLSs), frame a synovial microenvironment that responds to, augments and perpetuates the inflammatory process. Moreover, the FLSs have been recognised as the dominant cells mediating joint destruction. The identification of cadherin-11 expression on FLS provided an opportunity to unravel molecular mechanisms by which these resident mesenchymal cells govern processes that result in destructive synovitis in the context of systemic autoimmune disease. Herein, we discuss the unfolding biology of the synovial cadherin with its implications for the synovial pathology in arthritis, especially rheumatoid arthritis.