Therapeutic Potential of VEGI/TL1A in Autoimmunity and Cancer

Vascular endothelial growth inhibitor (VEGI, TNFSF-15) is a novel member of the tumor necrosis factor (TNF) superfamily that consists of 174 amino acids and exhibits a 20% to 30% sequence homology to other members of the TNF superfamily. The VEGI gene is expressed as a transmembrane protein predominantly in endothelial cells and induced generally in response to inflammatory stimuli. It mediates most of its cellular responses through the interaction of the death receptor-3. VEGI activates multiple cell signaling pathways including NF-kappaB, STAT3, JNK, p38 MAPK and p42/p44 MAPK. VEGI suppresses the proliferation of endothelial cells and tumor cells, induces maturation of dendritic cells and induces osteoclastogenesis. How VEGI mediates its effects in autoimmune diseases and tumorigenesis is the focus of this review.