TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator

Immunity. 2002 Mar;16(3):479-92. doi: 10.1016/s1074-7613(02)00283-2.

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

  • Amino Acid Sequence
  • Animals
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Ligands
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins*
  • Mice
  • Molecular Sequence Data
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / metabolism*
  • 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 / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1
  • Ligands
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Member 6b
  • TNFRSF25 protein, human
  • TNFRSF6B protein, human
  • TNFSF15 protein, human
  • Tnfrsf25 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Tumor Necrosis Factor-alpha