Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice
- 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.
Author: | Selina Christen, Ken Coppieters, Kerstin Rose, Martin Holdener, Monika Bayer, Josef PfeilschifterGND, Edith HintermannORCiDGND, Matthias G. von HerrathGND, Michel Aurrand-Lions, Beat A. Imhof, Urs ChristenORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-287070 |
DOI: | https://doi.org/10.1371/journal.pone.0054675 |
ISSN: | 1932-6203 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/23372751 |
Parent Title (English): | PLoS One |
Publisher: | PLoS |
Place of publication: | Lawrence, Kan. |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2013/01/29 |
Date of first Publication: | 2013/01/25 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/01/29 |
Volume: | 8 |
Issue: | 1: e54675 |
Page Number: | 13 |
Note: | 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. |
HeBIS-PPN: | 327381701 |
Institutes: | Medizin / Medizin |
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) | |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 3.0 |