TNF-related apoptosis-inducing ligand (TRAIL) in rheumatoid arthritis: what's new?

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein of the TNF superfamily that serves as an extracellular signal that triggers programmed cell death in tumor cells, without affecting normal cells. Recently, scientists have turned their attention to the emerging role of TRAIL in immune and autoimmune responses. TRAIL has been shown to down-regulate the self-antigens in autoimmune diseases, such as rheumatoid arthritis (RA) by exerting its apoptotic effect on activated T cells and synoviocytes and by its local anti-inflammatory effect. The impact of TRAIL molecular variants and agonistic monoclonal antibodies in the regulation of TRAIL activity in arthritis animal models strongly supports the idea of testing the role of TRAIL in humans, with the aim of developing new effective therapies that promote apoptosis of synoviocytes and/or infiltrating lymphocytes, by targeting TRAIL. The aim of this review is to summarize recent progress and current knowledge of TRAIL functions in RA.