title: In vitro studies implicate an imbalanced activation of dendritic cells in the pathogenesis of murine autoimmune pancreatitis.
abstract: OBJECTIVE
  MRL/MpJ mice spontaneously develop an autoimmune pancreatitis (AIP) and are widely used as a model to study the genetic, molecular and immunological basis of the disease. Here, we have addressed the question whether distinctive features of their dendritic cells (DCs) may predispose MRL/MpJ mice to the chronic inflammation.
  
  
  METHODS
  Pancreatic lesions were analyzed employing histological methods. Cohorts of young (healthy) MRL/MpJ mice, adult (sick) individuals, and AIP-resistant CAST/EiJ mice were used to establish cultures of bone marrow (BM)-derived conventional DCs (cDCs). The cells were subsequently characterized regarding the expression profile of CD markers and selected genes, proliferative activity as well as cytokine secretion.
  
  
  RESULTS
  In pancreatic lesions, large numbers of cells expressing the murine DC marker CD11c were detected in close spatial proximity to CD3+ cells. A high percentage of BM-derived cDCs from adult MRL/MpJ mice expressed typical markers of DC maturation (such as CD83) already prior to a treatment with lipopolysaccharide (LPS). After LPS-stimulation, cDC cultures of both MRL/MpJ mouse cohorts contained more mature cells, proliferated at a higher rate and secreted less interleukin-10 (but also less pro-inflammatory cytokines) than cultures of CAST/EiJ mice. Compared with corresponding cultures of the control strain, LPS-free cultured cDCs from MRL/MpJ mice expressed less mRNA of the inhibitory receptor triggering receptor expressed on myeloid cells 2 (trem2).
  
  
  CONCLUSIONS
  BM-derived cDCs from AIP-prone MRL/MpJ mice display functional features that are compatible with the hypothesis of an imbalanced DC activation in the context of murine AIP.
authors.affiliation: Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Luise
authors.initials: L
authors.lastname: Borufka
authors.affiliation: Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Volmer
authors.affiliation: Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Müller
authors.affiliation: Institute of Immunology and Core Facility for Cell Sorting & Cell Analysis, Rostock University Medical Center, Rostock, Germany.
authors.forename: Robby
authors.initials: R
authors.lastname: Engelmann
authors.affiliation: Institute of Pathology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Nizze
authors.affiliation: Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Saleh
authors.initials: S
authors.lastname: Ibrahim
authors.affiliation: Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Jaster
mesh_terms: D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008297:Male; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D008070:Lipopolysaccharides
keywords: Immune response; Immunity; Immunology and Microbiology Section; autoimmune pancreatitis; cell culture; dendritic cells; gene expression; mouse model