TL1A is a ligand belonging to the tumor necrosis factor (TNF) family (also called TNFSF15). It is expressed predominantly by endothelial cells and monocytes. TL1A is upregulated by the proinflammatory cytokines TNFα and IL-1ß and also by immune complexes (IC). TL1A functions in T cell costimulation and Th1 polarization. On activated T cells, TL1A functions specifically via its surface-bound receptor DR3, (a member of the deathdomain containing TNF receptor family) to promote cell survival and secretion of proinflammatory cytokines. The secreted decoy receptor 3 (DcR3), a soluble protein of the tumor necrosis factor receptor (TNFR) superfamily blocks the action of TL1A. TL1A can be released to circulate as a homotrimeric soluble form.

Activation of DR3 by TL1A induces the formation of a signaling complex containing TRADD, TRAF2, and RIP and activates the NF-?B and the ERK, JNK, and p38 mitogen-activated protein kinase pathways. The TL1A/DR3 pathway plays an important role in Th1-mediated intestinal diseases, such as Crohn’s disease. TL1A expression is increased in inflammatory bowel disease (IBD) and levels of TL1A protein as well as the number of TL1A-expressing cells correlate with the severity of inflammation, most significantly in Crohn's Disease.