Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Sara Tellefsen; Mathias Kaurstad Morthen; Stephen M Richards; Scott M Lieberman; Raheleh Rahimi Darabad; Wendy R Kam; David A Sullivan

doi:10.1167/iovs.18-25772

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Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Journal article

Open access

Peer reviewed

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Sara Tellefsen, Mathias Kaurstad Morthen, Stephen M Richards, Scott M Lieberman, Raheleh Rahimi Darabad, Wendy R Kam and David A Sullivan

Investigative ophthalmology & visual science, Vol.59(13), pp.5599-5614

11/01/2018

DOI: 10.1167/iovs.18-25772

PMCID: PMC6262646

PMID: 30481277

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https://doi.org/10.1167/iovs.18-25772View

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Abstract

Sjögren 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. 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. 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 Sjögren 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. These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.

Animals

Antigen Presentation - genetics

Autoimmune Diseases - metabolism

Chemokines - genetics

Disease Models, Animal

Female

Gene Expression Regulation - physiology

Inflammation - genetics

Lacrimal Apparatus - metabolism

Male

Mice

Mice, Inbred MRL lpr

Mice, Inbred NOD

RNA, Messenger - genetics

Sex Factors

Sjogren's Syndrome - metabolism

Details

Title: Subtitle: Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome
Creators: Sara Tellefsen - Oslo University Hospital
Mathias Kaurstad Morthen - Oslo University Hospital
Stephen M Richards - The University of Adelaide
Scott M Lieberman - University of Iowa
Raheleh Rahimi Darabad - Indiana University
Wendy R Kam - Harvard University
David A Sullivan - Harvard University
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.59(13), pp.5599-5614
DOI: 10.1167/iovs.18-25772
PMID: 30481277
PMCID: PMC6262646
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 1552-5783
eISSN: 1552-5783
Grant note: R01 EY005612 / NEI NIH HHS
Language: English
Date published: 11/01/2018
Academic Unit: Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
Record Identifier: 9984354051502771

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