Role of TRAIL in inflammatory bowel disease

TRAIL (TNF-related apoptosis-inducing ligand) is a type II transmembrane protein that belongs to TNF family, and it can induce apoptosis through binding with TRAIL receptor (TRAIL-R). TRAIL is widely expressed on activated immune cells, including NK cells, NKT, monocytes, DCs, T cells and B cells. Apart from inducing cell apoptosis, reports have suggested that TRAIL may play a role in regulation of autoimmunity. In autoimmune disease animal models such as EAE (experimental autoimmune encephalomyelitis) and streptozotocin (STZ) -induced diabetes, TRAIL-/- mice suffered more severe inflammation and accelerated pathogenesis. Moreover, our preliminary results showed that injection of recombinant TRAIL significantly reduced the severity of inflammation and may suppress the activation of T cell in CIA (collagen induced arthritis) mice. Based on these findings, we would like to investigate the role of TRAIL on other autoimmune disease. Inflammatory bowel disease (IBD) is an autoimmune disease caused by immune dysregulation, which leads to defective host immune tolerance toward commensal intestinal microbiota, and effects on intestinal epithelial barrier function. Although the role of TRAIL in IBD pathogenesis remained unclear, it has been reported that TRAIL-R-/- mice suffered more severe colitis in DSS-induced colitis, a widely use experimental IBD model. In addition, the importance of T cell in the pathogenesis of DSS-induced colitis has been well addressed. Therefore, we applied DSS-induced colitis to investigate the role of TRAIL in inflammatory colitis. Injection of recombinant TRAIL into DSS colitis mice significantly reduced DSS-induced weight loss, colon inflammation and epithelial damage. These result implied that TRAIL may promote anti-inflammatory response. However, the expression of both pro-inflammatory and anti-inflammatory cytokines are significantly down-regulated in colon tissue, suggesting that TRAIL may have direct effects on T cells. On the other hand, we found that the protective function of TRAIL was abolished in TRAIL-R-/- mice, indicating the therapeutic effect of TRAIL is dependent on the interaction with TRAIL-R. Further studies showed that TRAIL/TRAIL-R did not trigger apoptosis of either T cells or other cells in the colonic tissue, but suppressed the activation of T cells instead. Here we found that TRAIL plays an important role in IBD pathogenesis through suppressing the activation of T cells, and it may also provide a new potential therapeutic strategy for IBD.