TY  - JOUR
A1  - Christen, Selina
A1  - Coppieters, Ken
A1  - Rose, Kerstin
A1  - Holdener, Martin
A1  - Bayer, Monika
A1  - Pfeilschifter, Josef
A1  - Hintermann, Edith
A1  - Herrath, Matthias G. von
A1  - Aurrand-Lions, Michel
A1  - Imhof, Beat A.
A1  - Christen, Urs
T1  - Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice
T2  - PLoS One
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28707
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-287070
SN  - 1932-6203
N1  - Copyright: © 2013 Christen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 8
IS  - 1: e54675
PB  - PLoS
CY  - Lawrence, Kan.
ER  -