title: Changes in the Submandibular Salivary Gland Epithelial Cell Subpopulations During Progression of Sjögren's Syndrome-Like Disease in the NOD/ShiLtJ Mouse Model.
abstract: 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.
authors.affiliation: Department of Biological Sciences, State University of New York, University at Albany, Albany, New York.|Molecular, Cellular, Developmental, and Neural Biology Graduate Program, State University of New York, University at Albany, Albany, New York.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Gervais
authors.affiliation: Department of Biological Sciences, State University of New York, University at Albany, Albany, New York.|Molecular, Cellular, Developmental, and Neural Biology Graduate Program, State University of New York, University at Albany, Albany, New York.
authors.forename: Kara A
authors.initials: KA
authors.lastname: Desantis
authors.affiliation: Department of Biological Sciences, State University of New York, University at Albany, Albany, New York.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pagendarm
authors.affiliation: Department of Biological Sciences, State University of New York, University at Albany, Albany, New York.
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Nelson
authors.affiliation: Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Enger
authors.affiliation: Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.
authors.forename: Kathrine
authors.initials: K
authors.lastname: Skarstein
authors.affiliation: Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.
authors.forename: Janicke
authors.initials: J
authors.lastname: Liaaen Jensen
authors.affiliation: Department of Biological Sciences, State University of New York, University at Albany, Albany, New York.
authors.forename: Melinda
authors.initials: M
authors.lastname: Larsen
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D053569:Keratin-15 / Q000378:metabolism; D053555:Keratin-5 / Q000378:metabolism; D008297:Male; D016688:Mice, Inbred NOD; D008875:Middle Aged; D010641:Phenotype; D016111:Sjogren-Larsson Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013363:Submandibular Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers; C503940:KRT5 protein, human; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse
keywords: NOD/ShiLtJ; Sjögren's syndrome; cytokeratin 5; mouse; salivary gland