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.
MeSH terms
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Amino Acid Sequence
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Animals
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Humans
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Interleukin-1 / genetics
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Interleukin-1 / metabolism
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Ligands
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Lymphocyte Activation / immunology
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Membrane Glycoproteins*
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Mice
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Molecular Sequence Data
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor, Member 25
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Receptors, Tumor Necrosis Factor, Member 6b
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Sequence Alignment
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T-Lymphocytes / immunology
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Tumor Necrosis Factor Ligand Superfamily Member 15
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Tumor Necrosis Factor-alpha / genetics*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Interleukin-1
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Ligands
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 25
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Receptors, Tumor Necrosis Factor, Member 6b
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TNFRSF25 protein, human
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TNFRSF6B protein, human
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TNFSF15 protein, human
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Tnfrsf25 protein, mouse
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Tumor Necrosis Factor Ligand Superfamily Member 15
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Tumor Necrosis Factor-alpha