Fibroblasts and synovial immunity

Rheumatoid arthritis (RA) synovium is characterised not only by increases in number and activity of lymphocytes and macrophages, but also of resident mesenchymal cells known as fibroblast-like synoviocytes (FLS). Originally thought of as passive structural cells, research over two decades has demonstrated the capacity for autonomous contributions of FLS to RA inflammation as effector cells producing cytokines and other pro-inflammatory mediators. More recently, as understanding of RA as a genuine autoimmune disease characterised by immunity to citrullinated proteins has grown, so the potential involvement of FLS in even proximal aspects of initiation and maintenance of abnormal adaptive immune responses has come to light. In this review we take a step-by-step approach to the role of FLS, considering their contribution to the phenomena, as currently understood, in RA pathogenesis. It can be concluded that significant evidence favours a broad role for FLS in synovial immunity, as well as inflammation.