UNIGE document Scientific Article
previous document  unige:33959  next document
add to browser collection
Title

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

Authors
Christen, Selina
Coppieters, Ken
Rose, Kerstin
Holdener, Martin
Bayer, Monika
Pfeilschifter, Josef M
Hintermann, Edith
von Herrath, Matthias G
show hidden authors show all authors [1 - 11]
Published in PLOS ONE. 2013, vol. 8, no. 1, p. 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
Identifiers
PMID: 23372751
Full text
Article (Published version) (2.9 MB) - public document Free access
Structures
Research group Molécules d'adhésion et processus de migration cellulaire (167)
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. https://archive-ouverte.unige.ch/unige:33959

215 hits

277 downloads

Update

Deposited on : 2014-01-31

Export document
Format :
Citation style :