en
Scientific article
Open access
English

Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice

Published inPloS one, vol. 8, no. 1, e54675
Publication date2013
Abstract

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta-cells in the pancreas. Recruitment of inflammatory cells is prerequisite to beta-cell-injury. The junctional adhesion molecule (JAM) family proteins JAM-B and JAM-C are involved in polarized leukocyte transendothelial migration and are expressed by vascular endothelial cells of peripheral tissue and high endothelial venules in lympoid organs. Blocking of JAM-C efficiently attenuated cerulean-induced pancreatitis, rheumatoid arthritis or inflammation induced by ischemia and reperfusion in mice. In order to investigate the influence of JAM-C on trafficking and transmigration of antigen-specific, autoaggressive T-cells, we used transgenic mice that express a protein of the lymphocytic choriomeningitis virus (LCMV) as a target autoantigen in the β-cells of the islets of Langerhans under the rat insulin promoter (RIP). Such RIP-LCMV mice turn diabetic after infection with LCMV. We found that upon LCMV-infection JAM-C protein was upregulated around the islets in RIP-LCMV mice. JAM-C expression correlated with islet infiltration and functional beta-cell impairment. Blockade with a neutralizing anti-JAM-C antibody reduced the T1D incidence. However, JAM-C overexpression on endothelial cells did not accelerate diabetes in the RIP-LCMV model. In summary, our data suggest that JAM-C might be involved in the final steps of trafficking and transmigration of antigen-specific autoaggressive T-cells to the islets of Langerhans.

Keywords
  • Animals
  • Antibodies, Monoclonal/immunology
  • Antibodies, Neutralizing/immunology
  • Autoantigens/genetics/immunology
  • Cell Line
  • Diabetes Mellitus, Type 1/genetics/immunology/virology
  • Endothelial Cells/metabolism
  • Female
  • Gene Expression
  • Islets of Langerhans/immunology/pathology/virology
  • Junctional Adhesion Molecule C/antagonists & inhibitors/genetics/immunology
  • Lymphocytic choriomeningitis virus/immunology/pathogenicity
  • Male
  • Mice
  • Mice, Transgenic
  • T-Lymphocytes/immunology
Citation (ISO format)
CHRISTEN, Selina et al. Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice. In: PloS one, 2013, vol. 8, n° 1, p. e54675. doi: 10.1371/journal.pone.0054675
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1932-6203
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430downloads

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