Synovial fibroblasts: key players in rheumatoid arthritis.
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.
Center of Experimental Rheumatology, University Hospital Zurich, Gloriastrasse 23CH-8091 Zürich, Switzerland. lars.huber@usz.ch
L C
LC
Huber
O
O
Distler
I
I
Tarner
R E
RE
Gay
S
S
Gay
T
T
Pap
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle; D005109:Extracellular Matrix / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D006801:Humans; D013583:Synovial Membrane / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors