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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


  • 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
  • Wei P



Publication Data

March 25, 2002

Associated Grants


Mesh Terms

  • 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