Changes in the Submandibular Salivary Gland Epithelial Cell Subpopulations During Progression of S jögren's Syndrome‐Like Disease in the NOD / S hi L t J Mouse Model

• Published in: Anatomical record (Hoboken, N.J. : 2007) N.J. : 2007), 2015-09, Vol.298 (9), p.1622-1634
• Main Authors: Gervais, Elise M., Desantis, Kara A., Pagendarm, Nicholas, Nelson, Deirdre A., Enger, Tone, Skarstein, Kathrine, Liaaen Jensen, Janicke, Larsen, Melinda
• Format: Article
• Language: English
• ISSN: 1932-8486; 1932-8494
• DOI: 10.1002/ar.23190

Sjögren's syndrome (SS), an autoimmune exocrinopathy, is associated with dysfunction of the secretory salivary gland epithelium, leading to xerostomia. The etiology of SS disease progression is poorly understood as it is typically not diagnosed until late stage. Since mouse models allow the study of disease progression, we investigated the NOD/ShiLtJ mouse to explore temporal changes to the salivary epithelium. In the NOD/ShiLtJ model, SS presents secondary to autoimmune diabetes, and SS disease is reportedly fully established by 20 weeks. We compared epithelial morphology in the submandibular salivary glands (SMG) of NOD/ShiLtJ mice with SMGs from the parental strain at 12, 18, and 22 weeks of age and used immunofluorescence to detect epithelial proteins, including the acinar marker, aquaporin 5, ductal cell marker, cytokeratin 7, myoepithelial cell marker, smooth muscle α‐actin, and the basal cell marker, cytokeratin 5, while confirming immune infiltrates with CD45R. We also compared these proteins in the labial salivary glands of human SS patients with control tissues. In the NOD/ShiLtJ SMG, regions of lymphocytic infiltrates were not associated with widespread epithelial tissue degradation; however, there was a decrease in the area of the gland occupied by secretory epithelial cells in favor of ductal epithelial cells. We observed an expansion of cells expressing cytokeratin 5 within the ducts and within the smooth muscle α‐actin + basal myoepithelial population. The altered acinar/ductal ratio within the NOD/ShiLtJ SMG likely contributes to salivary hypofunction, while the expansion of cytokeratin 5 positive‐basal cells may reflect loss of function or indicate a regenerative response. Anat Rec, 298:1622–1634, 2015. © 2015 Wiley Periodicals, Inc.