DR3/TNFRSF25 His Tag Protein, Human

DR3 (TNFRSF25), a member of the tumor necrosis factor receptor superfamily, is a type I transmembrane glycoprotein characterized by an extracellular cysteine-rich domain that specifically binds its unique ligand TL1A (TNFSF15) and an intracellular death domain capable of recruiting the adaptor protein TRADD to activate downstream NF-κB and MAPK signaling pathways. Functionally, DR3 exerts bidirectional immunomodulatory effects: it maintains Foxp3⁺ regulatory T cell homeostasis to restrain excessive inflammation, while simultaneously promoting pathogenic Th17 differentiation and inducing fibroblast activation, contributing to intestinal fibrosis; genetic polymorphisms in its ligand-encoding gene TNFSF15 have been strongly associated with susceptibility to Crohn's disease and rheumatoid arthritis. Clinically, DR3 agonists are being developed for the treatment of autoimmune diseases and the prevention of graft-versus-host disease, whereas blocking antibodies show therapeutic promise in inflammatory bowel disease and fibrotic complications; moreover, enrichment of DR3⁺ Tregs in the tumor microenvironment correlates with immune evasion and poor prognosis, positioning DR3 as a multifaceted therapeutic target across autoimmunity, transplantation, oncology, and infectious diseases.