Abstract
BACKGROUND: Sjögren's Disease (SjD) is a chronic autoimmune condition characterized by lymphocytic infiltration of lacrimal glands (LG) and salivary glands (SG). In SG, these immune structures have properties of ectopic lymphoid structures (ELS) and appear to play a critical role in disease pathology. While the presence of ELS in patients' SG biopsies is linked to disease severity, their presence and composition in LG has not been well characterized. METHODS: The properties and time course of apparent ELS development in LG from the male non-obese diabetes free (NOR) sub-strain of the Non-Obese Diabetic (NOD) mice was investigated at stages encompassing early to advanced lymphocytic infiltration. LG ELS were characterized morphologically by histology and immunofluorescence. Changes in LG gene expression were determined for genes involved in ELS formation and maturation, LG homeostasis and LG apoptosis. RESULTS: LG ELS were characterized by segregation of B and T cell zones and the presence of high endothelial venules, follicular dendritic centers, GL7+ germinal center B cells, and IgG producing plasma cells. Gene expression data showed early upregulation of ELS indicators such as Ltb, Glycam1, Cxcl13, Cxcr5, Ccl19 and Ccr7 while other components showed elevation at later stages (Aicda and Il21). Increased Fasl and decreased Gpx4 expression suggested glandular apoptosis and ferroptosis concomitant with ELS formation. CONCLUSION: ELS form spontaneously in the LG of the male NOR mouse model of SjD and can recapitulate features of secondary lymphoid organs potentially acting as drivers of autoimmunity to sustain local glandular disease.