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Stromal cells as new therapeutic targets in rheumatoid arthritis

Oliver Haworth, Angela Burman, Greg Parsonage, Andrew Filer, Mike Salmon and Christopher D Buckley

Rheumatoid arthritis is a painful, debilitating disease in which inflammation is localized mainly to synovial joints. Despite a plethora of therapies targeted at inflammatory cells such as lymphocytes, there has been little impact made on affecting a cure. Even with the most effective current treatments (antitumor necrosis factor-α agents), only about 50% of patients gain a 70% response as measured by conventional disease activity criteria (ARC 70). In recent years, stromal cells that define the microenvironment in which inflammation occurs have been shown to play an important role in the pathogenesis of rheumatoid arthritis, especially during the switch from acute to chronic persistent disease. In this review, the role that stromal cells, such as endothelial cells, fibroblasts and macrophages play in the pathogenesis of rheumatoid arthritis are examined, and it is suggested that these cells in addition to inflammatory immune cells provide an important and underappreciated therapeutic target.