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The Junctional Adhesion Molecule JAM-C

 



Selina Christen, Edith Hintermann, Monika Bayer and Urs Christen

 

In collaboration with:

Beat A. Imhof (Centre Médical Universitaire, Geneva, Switzerland)

Michel Aurrand-Lions (Inserm, CNRS, Aix-Marseille Université, Marseille, France)

Matthias G. von Herrath and Ken Coppetiers (La Jolla Institute for Allergy and Immunology, San Diego, California, USA)

 

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 b-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.

 

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

Christen et al (2013) PLoS One (in press)