Abstracts (complete list) - Wissenschaft Online

Selina Christen, Edith Hintermann, Monika Bayer, Urs Christen
JAM-C and its influence on the pathogenesis of type 1 diabetes
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing
beta-cells in the pancreas. Recruitment of inflammatory cells, such as T-cells, B-cells
and dendritic cells is prerequisite to beta-cell-injury. Such a process includes several
molecular interactions between circulating and endothelial cells. The junctional adhesion
molecule (JAM) family proteins JAM-B and JAM–C, are expressed on endothelial cells of
high endothelial vessels and appear to be involved in leukocyte rolling, firm adhesion
and transmigration. It was recently demonstrated that after blocking of JAM-C ceruleininduced
pancreatitis was efficiently attenuated in mice. Early intervention with a
monoclonal antibody directed against JAM-C reduced cytokine production, leukocyte
influx, and hence tissue damage.
In order to investigate the influence of JAM-C on trafficking and transmigration of
antigen-specific, autoaggressive T-cells we used the RIP-LCMV mice as a model system.
These mice express the nucleoprotein (NP) of lymphocytic choriomeningitis virus
(LCMV) as a target autoantigen specifically in the beta-cells of the islets of Langerhans
and turn diabetic after LCMV infection. In such diabetic RIP-LCMV mice the expression
of JAM-C is detectable around the vessels within the pancreas. Interestingly,
immunohistological evaluation of pancreas sections revealed that JAM-C was expressed
directly in between cellular infiltrations and beta-cells.
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 and
might therefore play an important role in the pathogenesis of T1D.