TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.
DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1alpha. TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events. Interestingly, in T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines both in vitro and in vivo. Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect.
Pubmed ID: 11911831 RIS Download
Amino Acid Sequence | Animals | Humans | Interleukin-1 | Ligands | Lymphocyte Activation | Membrane Glycoproteins | Mice | Molecular Sequence Data | Receptors, Cell Surface | Receptors, Tumor Necrosis Factor | Receptors, Tumor Necrosis Factor, Member 25 | Receptors, Tumor Necrosis Factor, Member 6b | Sequence Alignment | T-Lymphocytes | Tumor Necrosis Factor Ligand Superfamily Member 15 | Tumor Necrosis Factor-alpha