Natural killer T cells mediate inflammation in the bile ducts

Mucosal Immunol. 2018 Nov;11(6):1582-1590. doi: 10.1038/s41385-018-0066-8. Epub 2018 Aug 16.


Cholangiocytes function as antigen-presenting cells with CD1d-dependent activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro- and anti-inflammatory in liver immunopathology. We explored this immune pathway and the antigen-presenting potential of NKT cells in the bile ducts by challenging wild-type and Cd1d-/- mice with intrabiliary injection of the NKT cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated activation was performed with a monoclonal antibody. Intrabiliary oxazolone injection in wild-type mice caused acute cholangitis with significant weight loss, elevated serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin, increased histologic grade of cholangitis and number of T cells, macrophages, neutrophils and myofibroblasts per portal tract after 7 days. NKT cells were activated after intrabiliary injection of oxazolone with upregulation of activation markers. Cd1d-/- and wild-type mice pretreated with antibody blocking of CD1d were protected from disease. These findings implicate that cells in the bile ducts function as antigen-presenting cells in vivo and activate NKT cells in a CD1d-restricted manner. The elucidation of this biliary immune pathway opens up for potentially new therapeutic approaches for cholangiopathies.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • Antigen Presentation
  • Antigens, CD1d / genetics
  • Antigens, CD1d / immunology
  • Antigens, CD1d / metabolism
  • Bile Ducts / pathology*
  • Cells, Cultured
  • Cholangitis / immunology*
  • Epithelial Cells / immunology*
  • Female
  • Humans
  • Immunization
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Oxazolone / administration & dosage


  • Antibodies, Blocking
  • Antigens, CD1d
  • CD1d antigen, mouse
  • Oxazolone