Defective E-cadherin adhesion in the salivary glands from Sjogren's patients

Objectives: Sjogren's syndrome (SS) is an autoimmune systemic disease characterized by lymphocytic infiltration of lacrimal and salivary glands. In the present study, we investigated intercellular adhesion in labial salivary glands from individuals diagnosed with SS. We focused on two major junctional complexes that affect cell-cell adhesion: E-cadherin-mediated adherens junctions (AJs) and ZO-1 containing tight junctions (TJs). AJs determine the strength of adhesion and their stabilization drives the assembly of TJs at the apical domains where they form a paracellular permeability barrier in polarized epithelia. Methods: Formalin fixed and paraffin-embedded tissue samples from the biopsies of minor salivary glands were examined by indirect immunofluorescence and confocal microscopy for tissue integrity and morphology. Results: Salivary tissues of individuals diagnosed with SS in comparison to those not compatible with SS displayed aberrant morphology and smaller cell size. This correlated with significant changes in immunolocalization of AJs. In addition, in the SS-compatible cases, E-cadherin was frequently diminished from the lateral-apical domains. This was accompanied by an apparent lack of TJs at the apical surfaces, as evidenced by the absence of ZO-1 in SS tissues. Conclusion: Minor salivary glands from SS-compatible patients revealed distinct phenotypes that included altered E-cadherin adhesion and defective TJs, both of which could be responsible for smaller cell size and abnormal morphology of the glands. Hence, aberrant intercellular adhesion appears to be one of the contributing factors to lymphocytic infiltration and xerostomia in SS. This work was supported by Grants DE14437 and DE10183 from the NIH/NIDCR to MAK