Oncotarget

Research Papers: Immunology:

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

Luise Borufka, Erik Volmer, Sarah Müller, Robby Engelmann, Horst Nizze, Saleh Ibrahim and Robert Jaster _

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Oncotarget. 2016; 7:42963-42977. https://doi.org/10.18632/oncotarget.10265

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Abstract

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

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.


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