title: A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.
abstract: Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.|ISIM- Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Fransén-Pettersson
authors.affiliation: Department of Medical Bioscience-Medical Genetics, Umeå University, 901 85 Umeå, Sweden.|Instituto Gulbenkian de Sciencia, Oeiras, 2780-156 Oeiras, Portugal.
authors.forename: Nadia
authors.initials: N
authors.lastname: Duarte
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Department of Medical Bioscience-Medical Genetics, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Lundholm
authors.affiliation: Department of Medical Bioscience-Medical Genetics, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mayans
authors.affiliation: Department of Medical Bioscience-Medical Genetics, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Larefalk
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.|ISIM- Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark.
authors.forename: Tine D
authors.initials: TD
authors.lastname: Hannibal
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.|ISIM- Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Hansen
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmidt-Christensen
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ivars
authors.affiliation: Institute for Biomedicine-Infection and Immunology, University of Gothenburg, 405 30, Göteborg, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cardell
authors.affiliation: Department of Medical Bioscience-Pathology, Faculty of Medicine, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.affiliation: Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Rozell
authors.affiliation: EMV Immunology, BMC, Lund University, 221 00 Lund, Sweden.|ISIM- Immunology, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark.|Department of Medical Bioscience-Medical Genetics, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Dan
authors.identifier: http://orcid.org/0000-0002-5645-3514
authors.initials: D
authors.lastname: Holmberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006521:Hepatitis, Chronic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators