Synovial fibroblasts as potential drug targets in rheumatoid arthritis, where do we stand and where shall we go?

Fibroblast-like synoviocytes or synovial fibroblasts (FLS) are important cellular components of the inner layer of the joint capsule, referred to as the synovial membrane. They can be found in both layers of this synovial membrane and contribute to normal joint function by producing extracellular matrix components and lubricants. However, under inflammatory conditions like in rheumatoid arthritis (RA), they may start to proliferate, undergo phenotypical changes and become central elements in the perpetuation of inflammation through their direct and indirect destructive functions. Their importance in autoimmune joint disorders makes them attractive cellular targets, and as mesenchymal-derived cells, their inhibition may be carried out without immunosuppressive consequences. Here, we aim to give an overview of our current understanding of the target potential of these cells in RA.