Language
English
Publication Date
1-1-2022
Journal
Frontiers in Medicine
DOI
10.3389/fmed.2022.849990
PMID
35402439
PMCID
PMC8983848
PubMedCentral® Posted Date
3-23-2022
PubMedCentral® Full Text Version
Post-print
Abstract
PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.
METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.
RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear volume, corneal barrier disruption, corneal/conjunctival cornification and goblet cell loss, and corneal vascularization, opacification, and ulceration with aging. ScRNA-seq of conjunctival immune cells identified γδ T cells as the predominant IL-17 expressing population in both strains and there is a 4-fold increased percentage of γδ T cells in Pinkie. Compared to WT, IL-17a, and IL-17f significantly increased in Pinkie with conventional T cells and γδ T cells as the major producers. Flow cytometry revealed an increased number of IL-17
CONCLUSION: These findings indicate that RXRα suppresses generation of dry eye disease-inducing IL-17 producing lymphocytes s in the conjunctiva and identifies RXRα as a potential therapeutic target in dry eye.
Keywords
gamma delta (gammadelta) T cells, conjunctiva, dry eye, IL-17, retinoic acid, RXR alpha
Published Open-Access
yes
Recommended Citation
Alam, Jehan; Yazdanpanah, Ghasem; Ratnapriya, Rinki; et al., "IL-17 Producing Lymphocytes Cause Dry Eye and Corneal Disease With Aging in RXRα Mutant Mouse" (2022). Faculty and Staff Publications. 2726.
https://digitalcommons.library.tmc.edu/baylor_docs/2726