TL1A/TNFSF15 Protein, Mouse

TL1A (Tumor necrosis factor-like cytokine 1A), also known as TNF ligand-related molecule 1 and vascular endothelial cell growth inhibitor (VEGI), is the receptor for TNFRSF25 and TNFRSF6B, acts as a regulator of mucosal immunity and participates in immunological pathways involved in the inflammatory bowel diseases (IBD) pathogenesis^[1]. TL1A belongs to the tumor necrosis factor family, derived from endothelial cell. It is a ligand for DR3 and decoy receptor TR6/DcR3, the interaction with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect. Moreover, DR3 is the death domain-containing receptor, that is upregulated during T cell activation. TL1A shows an inducible expression by TNF and IL-1alpha, and induces NF-kappaB activation and apoptosis in DR3-expressing cell lines. Meanwhile, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines^[2]. In addition, TL1A activates c-Jun N-terminal kinase. TL1A also activates caspase-3 leading to PARP cleavage, and inhibits the proliferation of breast carcinoma, epithelial, and myeloid tumor cells. TL1A promotes proliferation of normal human fibroblast cells. These results suggest that VEGI, a new member of the TNF family, has a signaling pathway similar to TNF and is most likely a multifunctional cytokine^[3]. Mouse TL1A protein has two glycosylated domains and one transmembrane domain (36-56 a.a.), and can be cleaved into membrane-type peptide fragments and soluble peptide fragments. The protein sequence of mouse is much different from rat and human with similarities of 85.32% and 68.42%, respectively.