Regulation of Immune Responses and Chronic Inflammation by Fibroblast-Like Synoviocytes

Synovial tissue is a membranous non-immune organ lining joint cavities where it supports local immune responses, and functions directly and indirectly in joint destruction due to chronic inflammatory diseases such as rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS), the dominant non-immune cells of synovial tissues, mainly contribute to joint destruction via multiple mechanisms. In RA, FLS respond to endogenous ligands of pattern recognition receptors (PRRs) and inflammatory cytokines as non-immune cells. In addition, FLS aid in the activation of immune responses by interacting with immune cells and by supporting ectopic lymphoid-like structure (ELS) formation in synovial tissues. Moreover, FLS directly cause the pathogenicity of RA i.e., joint deformities. Here, we describe new findings and review the mechanisms underlying the regulation of immune reactions by non-immune FLS and their roles in inflammatory diseases such as RA.