Where ends the TRAIL in arthritis?

A hallmark of rheumatoid arthritis (RA) is the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLS), as these cells invade and finally destroy the joint structure. RA FLS have been proposed therefore as a therapeutic target. The TNF-related apoptosis-inducing ligand (TRAIL) has gained much attention as a possible therapeutic reagent for the treatment of tumors, as TRAIL was described originally to induce apoptosis specifically in cancer cells but not in normal cells. The fact that FLS in RA patients exhibit tumor-like features led to investigations on the effect of TRAIL on ex-vivo RA FLS. In this review we aim to summarize what is presently known on the role of TRAIL in RA.