Reduced levels of insulin-like growth factor-1 receptor (IGF-1R) suppress cellular signaling in experimental autoimmune sialadenitis (EAS)

The nonobese diabetic mouse (NOD) develops destruction and functional impai rment of salivary and lachrymal glands, experimental autoimmune sialadeniti s (EAS), resembling and representing a model for Sjogren's syndrome (SS). T o investigate the mechanisms of tissue destruction in EAS, we analyzed a ce ll survival promoter insulin-like growth factor-1 receptor (IGF-1R) in the submandibular glands of NOD mice with this disease. We also evaluated the e xpression of a downstream effector of IGF-1R, BAD. Receptor-binding autorad iography revealed that the IGF-1R levels in submandibular glands from young NOD mice were lower than those in adult NOD mice. Immunofluorescence stain ing demonstrated that BAD expression in the epithelial cells of the submand ibular gland was consistently enhanced throughout the course of EAS in NOD mice. These findings suggest that a reduction in the levels of IGF-1R induc es a defective glandular homeostasis in the submandibular gland epithelial cells and triggers EAS.