The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator

J Leukoc Biol. 2015 Sep;98(3):333-45. doi: 10.1189/jlb.3RI0315-095R. Epub 2015 Jul 17.


Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells. Noncoding variants in the TL1A locus are associated with susceptibility to inflammatory bowel disease and leprosy, predicting that the level of TL1A expression may influence host defense and the development of autoimmune and inflammatory diseases.

Keywords: DR3; autoimmune disease.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Disease Models, Animal
  • Humans
  • Lymphocyte Activation / immunology
  • Receptors, Death Domain / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / metabolism*


  • Receptors, Death Domain
  • Tumor Necrosis Factor Ligand Superfamily Member 15