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Hepatology. 2015 Oct;62(4):1249-59. doi: 10.1002/hep.27840. Epub 2015 May 20.

The biliary epithelium presents antigens to and activates natural killer T cells.

Author information

1
Norwegian PSC Research Center, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
2
K.G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
4
Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
5
K.G.Jebsen Inflammation Research Centre, Laboratory of Immunohistochemistry and Immunopathology, Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
6
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
7
Liver Immunology Laboratory, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
8
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
9
Department of Integrative Physiology and Pathobiology, Sackler School, Tufts University School of Medicine, Boston, MA.
10
Division of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.
11
Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
12
Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
13
Manchester Collaborative Centre for Inflammation Research, Faculty of Medical & Human Sciences, University of Manchester, Manchester, UK.
14
Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Abstract

Cholangiocytes express antigen-presenting molecules, but it has been unclear whether they can present antigens. Natural killer T (NKT) cells respond to lipid antigens presented by the major histocompatibility complex class I-like molecule CD1d and are abundant in the liver. We investigated whether cholangiocytes express CD1d and present lipid antigens to NKT cells and how CD1d expression varies in healthy and diseased bile ducts. Murine and human cholangiocyte cell lines as well as human primary cholangiocytes expressed CD1d as determined by flow cytometry and western blotting. Murine cholangiocyte cell lines were able to present both exogenous and endogenous lipid antigens to invariant and noninvariant NKT cell hybridomas and primary NKT cells in a CD1d-dependent manner. A human cholangiocyte cell line, cholangiocarcinoma cell lines, and human primary cholangiocytes also presented exogenous CD1d-restricted antigens to invariant NKT cell clones. CD1d expression was down-regulated in the biliary epithelium of patients with late primary sclerosing cholangitis, primary biliary cirrhosis, and alcoholic cirrhosis compared to healthy controls.

CONCLUSIONS:

Cholangiocytes express CD1d and present antigens to NKT cells and CD1d expression is down-regulated in diseased biliary epithelium, findings which show that the biliary epithelium can activate an important lymphocyte subset of the liver. This is a potentially important immune pathway in the biliary system, which may be capable of regulating inflammation in the context of biliary disease.

PMID:
25855031
PMCID:
PMC4589438
DOI:
10.1002/hep.27840
[Indexed for MEDLINE]
Free PMC Article

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