1. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.
- Author
-
Migone TS, Zhang J, Luo X, Zhuang L, Chen C, Hu B, Hong JS, Perry JW, Chen SF, Zhou JX, Cho YH, Ullrich S, Kanakaraj P, Carrell J, Boyd E, Olsen HS, Hu G, Pukac L, Liu D, Ni J, Kim S, Gentz R, Feng P, Moore PA, Ruben SM, and Wei P
- Subjects
- Amino Acid Sequence, Animals, Humans, Interleukin-1 genetics, Interleukin-1 metabolism, Ligands, Lymphocyte Activation immunology, Mice, Molecular Sequence Data, Receptors, Cell Surface immunology, Receptors, Tumor Necrosis Factor immunology, Receptors, Tumor Necrosis Factor, Member 25, Receptors, Tumor Necrosis Factor, Member 6b, Sequence Alignment, T-Lymphocytes immunology, Tumor Necrosis Factor Ligand Superfamily Member 15, Tumor Necrosis Factor-alpha metabolism, Membrane Glycoproteins, Receptors, Cell Surface metabolism, Receptors, Tumor Necrosis Factor metabolism, Tumor Necrosis Factor-alpha genetics
- Abstract
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.
- Published
- 2002
- Full Text
- View/download PDF