title: The role of natural killer T cells in a mouse model with spontaneous bile duct inflammation.
abstract: Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d-/-mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice. Activation or blocking of NKT cells withα-galactosylceramide or anti-CD1d antibody injections did not affect the biliary phenotype of NODc3c4 mice. NODc3c4.Cd1d-/-mice were generated by crossing NODCd1d-/-mice onto a NODc3c4 background. NODc3c4.Cd1d-/-and NODc3c4 mice developed the same extent of biliary disease. This study demonstrates that iNKT cells are more abundant and activated in the NODc3c4 model. The portal inflammation of NODc3c4 mice can be transferred to irradiated recipients, which suggests an immune-driven disease. Our findings imply that NKT cells can potentially participate in the biliary inflammation, but are not the primary drivers of disease in NODc3c4 mice.
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schrumpf
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Medicine 1, University Medical Center Dresden Technical University Dresden, Dresden, Germany.|Center for Regenerative Therapies (CRTD), Technical University Dresden, Dresden, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zeissig
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Research Unit for Experimental and Molecular Hepatology, Graz, Austria.|Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Pollheimer
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Jarl Andreas
authors.initials: JA
authors.lastname: Anmarkrud
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Corey
authors.initials: C
authors.lastname: Tan
authors.affiliation: Manchester Collaborative Centre for Inflammation Research (MCCIR), Faculty of Medical & Human Sciences, University of Manchester, Manchester, United Kingdom.|Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Exley
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway espen.melum@medisin.uio.no.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Melum
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics* / Q000276:immunology; D001649:Bile Duct Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide
keywords: 
  NKT
  ; 
  PBC
  ; 
  PSC
  ; Cholestasis; NOD.c3c4