Targeting fibroblast-like synoviocytes in rheumatoid arthritis

Abstract

Fibroblast-like synoviocytes (FLS) are mesenchymal-derived cells that play an important role in the physiology of the synovium by producing certain components of the synovial fluid and articular cartilage. In rheumatoid arthritis (RA), however, fibroblasts become a key driver of synovial inflammation and joint damage. Because of this, there has been recent interest in FLS as a therapeutic target in RA to avoid side effects such as systemic immune suppression associated with many existing RA treatments. In this review, we describe how approved treatments for RA affect FLS signaling and function and discuss the effects of investigational FLS-targeted drugs for RA.

Figure 1.

FLS signaling and function in RA. FLS have numerous effects on the synovial immune environment through production of cytokines, chemokines, and prostaglandins, and directly erode cartilage using MMP. Some approved drugs (green) and investigational drugs (red) for RA inhibit several important FLS functional pathways. Abbreviations: CCL2: C-C Motif Chemokine Ligand 2; CDK: cyclin-dependent kinase; GM-CSF: Granulocyte macrophage colony-stimulating factor; IL: interleukin; JAK: Janus kinase; IRAK4: interleukin-1 receptor-associated kinase 4; MMP: matrix metalloproteinase; RANKL: Receptor activator of nuclear factor kappa-B ligand; STAT: Signal transducer and activator of transcription; TNF: tumor necrosis factor;