The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases

Immunity. 2008 Jul 18;29(1):79-89. doi: 10.1016/j.immuni.2008.04.021. Epub 2008 Jun 19.


DR3 (TRAMP, LARD, WSL-1, TNFRSF25) is a death-domain-containing tumor necrosis factor (TNF)-family receptor primarily expressed on T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. Using DR3-deficient mice, we identified DR3 as the receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell activation. Despite its role in costimulation, DR3 was not required for in vivo T cell priming, for polarization into T helper 1 (Th1), Th2, or Th17 effector cell subtypes, or for effective control of infection with Toxoplasma gondii. Instead, DR3 expression was required on T cells for immunopathology, local T cell accumulation, and cytokine production in Experimental Autoimmune Encephalomyelitis (EAE) and allergic lung inflammation, disease models that depend on distinct effector T cell subsets. DR3 could be an attractive therapeutic target for T cell-mediated autoimmune and allergic diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Tumor Necrosis Factor, Member 25 / immunology*
  • Receptors, Tumor Necrosis Factor, Member 25 / metabolism
  • Respiratory Hypersensitivity / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Toxoplasmosis / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / metabolism


  • Receptors, Tumor Necrosis Factor, Member 25
  • Tnfrsf25 protein, mouse
  • Tnfsf15 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 15