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

Christen, Selina
Coppieters, Ken
Rose, Kerstin
Holdener, Martin
Bayer, Monika
Pfeilschifter, Josef M
Hintermann, Edith
von Herrath, Matthias G
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Published in PloS one. 2013, vol. 8, no. 1, e54675
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 AnimalsAntibodies, Monoclonal/immunologyAntibodies, Neutralizing/immunologyAutoantigens/genetics/immunologyCell LineDiabetes Mellitus, Type 1/genetics/immunology/virologyEndothelial Cells/metabolismFemaleGene ExpressionIslets of Langerhans/immunology/pathology/virologyJunctional Adhesion Molecule C/antagonists & inhibitors/genetics/immunologyLymphocytic choriomeningitis virus/immunology/pathogenicityMaleMiceMice, TransgenicT-Lymphocytes/immunology
PMID: 23372751
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Research group Molécules d'adhésion et processus de migration cellulaire (167)
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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 https://archive-ouverte.unige.ch/unige:33959

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Deposited on : 2014-01-31

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