Stroma: fertile soil for inflammation.

Biological therapies for the management of immune mediated inflammatory diseases such as rheumatoid arthritis have proven to be extremely successful in recent years. Despite these successes, even the most effective of therapies do not lead to cure. Why chronic inflammation persists indefinitely within the rheumatoid synovium despite an absence of continuous stimulation, and why some patients with early synovitis progress to persistent disease whilst others do not, has remained unexplained. In contrast to the paradigm that stromal cells are biochemically active but immunologically passive, there is now growing evidence that stromal components from the rheumatoid synovium play a crucial part in the immunopathology of rheumatoid arthritis. Stromal cells play a central role in the transformation of an acute, resolving to a chronic inflammatory process, and to the persistence of synovial inflammation and joint destruction through a variety of immune mechanisms. Therapeutic manipulation of the stroma is a largely unexplored, yet potentially vital area of research. Targeting pathogenic stromal cells has the potential to provide a cure for chronic inflammatory disorders such as rheumatoid arthritis.