Natural killer T cells mediate inflammation in the bile ducts View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-11

AUTHORS

N L Berntsen, B Fosby, C Tan, H M Reims, J Ogaard, X Jiang, E Schrumpf, L Valestrand, T H Karlsen, P-D Line, R S Blumberg, E Melum

ABSTRACT

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. More... »

PAGES

1582-1590

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41385-018-0066-8

DOI

http://dx.doi.org/10.1038/s41385-018-0066-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106154150

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30115993


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