Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis

Liver Int. 2014 May;34(5):679-88. doi: 10.1111/liv.12296. Epub 2013 Sep 9.


Background & aims: Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.

Methods: We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining.

Results: Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients.

Conclusions: These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.

Keywords: decoy receptor 3; primary biliary cirrhosis; tumour necrosis factor-like ligand 1A; ursodeoxycholic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antinuclear / blood
  • Case-Control Studies
  • Cholagogues and Choleretics / therapeutic use
  • Female
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis, Biliary / blood*
  • Liver Cirrhosis, Biliary / drug therapy
  • Liver Cirrhosis, Biliary / pathology
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor, Member 6b / blood*
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / blood*
  • Ursodeoxycholic Acid / therapeutic use


  • Antibodies, Antinuclear
  • Cholagogues and Choleretics
  • Receptors, Tumor Necrosis Factor, Member 6b
  • TNFRSF6B protein, human
  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Ursodeoxycholic Acid