Research Papers: Immunology:
In vitro studies implicate an imbalanced activation of dendritic cells in the pathogenesis of murine autoimmune pancreatitis
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Luise Borufka1, Erik Volmer1, Sarah Müller1, Robby Engelmann2, Horst Nizze3, Saleh Ibrahim4 and Robert Jaster1
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
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
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.
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