Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that 
primarily affects the joints and ultimately leads to their destruction. The 
involvement of immune cells is a general hallmark of autoimmune-related 
disorders. In this regard, macrophages, T cells and their respective cytokines 
play a pivotal role in RA. However, the notion that RA is a primarily 
T-cell-dependent disease has been strongly challenged during recent years. 
Rather, it has been understood that resident, fibroblast-like cells contribute 
significantly to the perpetuation of disease, and that they may even play a role 
in its initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) 
constitute a quite unique cell type that distinguishes RA from other 
inflammatory conditions of the joints. A number of studies have demonstrated 
that RASFs show alterations in morphology and behaviour, including molecular 
changes in signalling cascades, apoptosis responses and in the expression of 
adhesion molecules as well as matrix-degrading enzymes. These changes appear to 
reflect a stable activation of RASFs, which occurs independently of continuous 
exogenous stimulation. As a consequence, RASFs are no longer considered passive 
bystanders but active players in the complex intercellular network of RA.