1. Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome
- Author
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Wendy R. Kam, Scott M. Lieberman, David A. Sullivan, Raheleh Rahimi Darabad, Sara Tellefsen, Mathias Kaurstad Morthen, and S. M. Richards
- Subjects
0301 basic medicine ,sex differences ,Male ,Chemokine ,Mice, Inbred MRL lpr ,Nod ,Lacrimal gland ,Biology ,medicine.disease_cause ,Autoimmunity ,Autoimmune Diseases ,Cornea ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Sex Factors ,stomatognathic system ,Mice, Inbred NOD ,Gene expression ,medicine ,Animals ,RNA, Messenger ,NOD mice ,Autoimmune disease ,Inflammation ,Antigen Presentation ,Lacrimal Apparatus ,MRL/lpr-lpr/lpr mice ,medicine.disease ,nonobese diabetic mice ,Sjögren syndrome ,lacrimal gland ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Sjogren's Syndrome ,Gene Expression Regulation ,Immunology ,biology.protein ,gene expression ,Female ,Chemokines ,030217 neurology & neurosurgery - Abstract
Purpose Sjogren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjogren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjogren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.
- Published
- 2018