Publication Date
1-1-2022
Journal
Frontiers in Immunology
DOI
10.3389/fimmu.2022.1011125
PMID
36341342
PMCID
PMC9628215
PubMedCentral® Posted Date
10-17-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Mice, Animals, Lacrimal Apparatus, Mice, Inbred NOD, Transcriptome, Dry Eye Syndromes, Sjogren's Syndrome, Macrophages, Inflammation, Epithelium, lacrimal gland, chronic inflammation, visium, lipid metabolism, RNA sequencing, TYROBP, macrophages, spatial transcriptomics
Abstract
The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the first time, we analyzed and validated specific pathways defined by bulk RNAseq using Visium technology to determine activation of these pathways within the LG sections. This analysis suggests that altered metabolism and the hallmarks of inflammatory responses from both epithelial and immune cells drive inflammation. The most significant pathway enriched in upregulated DEGs was the “TYROBP Causal Network”, that has not been described previously in SS. We also noted a significant decrease in lipid metabolism in the LG of the NOD.H-2b mice. Our data suggests that modulation of these pathways can provide a therapeutic strategy to treat ADDE.
Included in
Eye Diseases Commons, Medical Sciences Commons, Ophthalmology Commons, Optometry Commons