Morthen, Mathias KaurstadTellefsen, SaraRichards, Stephen M.Lieberman, Scott M.Rahimi Darabad, RahelehKam, Wendy R.Sullivan, David A.2019-08-222019-08-222019-05Morthen, M. K., Tellefsen, S., Richards, S. M., Lieberman, S. M., Rahimi Darabad, R., Kam, W. R., & Sullivan, D. A. (2019). Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome. Investigative ophthalmology & visual science, 60(6), 2181–2197. doi:10.1167/iovs.19-26815https://hdl.handle.net/1805/20502Purpose: Sjögren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6lpr [MRL/lpr]) of Sjögren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain- and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. Methods: Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. Results: Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. Conclusions: Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesTestosteroneSjögren syndromeLacrimal glandGene expressionMRL/lpr-lpr/lpr miceNonobese diabetic miceArticle