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In vitro studies implicate an imbalanced activation of dendritic cells in the pathogenesis of murine autoimmune pancreatitis

2016; Impact Journals LLC; Volume: 7; Issue: 28 Linguagem: Inglês

10.18632/oncotarget.10265

1949-2553

Luise Borufka, Erik Volmer, Sarah Müller, R. Engelmann, Horst Nizze, Saleh Ibrahim, Robert Jaster,

Neuroendocrine Tumor Research Advances

// Luise Borufka 1 , Erik Volmer 1 , Sarah Müller 1 , Robby Engelmann 2 , Horst Nizze 3 , Saleh Ibrahim 4 and Robert Jaster 1 1 Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock, Germany 2 Institute of Immunology and Core Facility for Cell Sorting & Cell Analysis, Rostock University Medical Center, Rostock, Germany 3 Institute of Pathology, Rostock University Medical Center, Rostock, Germany 4 Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany Correspondence to: Robert Jaster, email: // Keywords : autoimmune pancreatitis, mouse model, dendritic cells, cell culture, gene expression, Immunology and Microbiology Section, Immune response, Immunity Received : April 14, 2016 Accepted : June 09, 2016 Published : June 23, 2016 Abstract Objectives: 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.