摘要
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation ofinflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocytes andinfiltrating lymphocytes. The aim of this study was to investigate the immunomodulatory mechanism and role ofTRAIL in inflammatory arthritis. We created an animal model of inflammatory arthritis and demonstrated that TRAILsignificantly inhibited joint inflammation and reduced the severity of arthritis. The suppression of joint inflammationwas not due to the TRAIL-mediated induction of apoptosis in T cells, macrophages or synovial fibroblasts. Incontrast, TRAIL directly inhibited T-cell proliferation and suppressed the production of cytokines, which indicatedthat TRAIL exerted its anti-inflammatory effects by direct inhibition of T-cell activation. Moreover, TRAIL receptor(TRAIL-R)-knockout mice developed more severe disease, and the protective effects of TRAIL were abolished in theexperimental arthritis model in TRAIL-R knockout mice. From these results, we conclude that TRAIL suppressesjoint inflammation via an apoptosis-independent pathway and directly inhibits T-cell activation. Our results providea novel apoptosis-independent, immune regulatory role for TRAIL in suppressing inflammatory arthritis and shedlight on the development of effective new therapies for autoimmune inflammatory diseases.
基金
This work was supported by grants from the National Science Council,Taiwan(NSC 101-2321-B-002-008 and 104-2314-B-281-002-,MOST 105-2320-B-002-034-and 105-2320-B-038-065-)。
