Conditional Deletion of CD25 in the Corneal Epithelium Reveals Sex Differences in Barrier Disruption
Publication Date
10-1-2023
Journal
The Ocular Surface
DOI
10.1016/j.jtos.2023.07.008
PMID
37516317
PMCID
PMC10812880
PubMedCentral® Posted Date
10-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Animals, Female, Male, Mice, Cornea, Epithelium, Corneal, Interleukin-2, Mice, Inbred C57BL, Mice, Knockout, Sex Characteristics, CD25, IL-2, cornea, dry eye, wound healing, sex, corneal barrier
Abstract
PURPOSE: IL-2 promotes activation, clonal expansion, and deletion of T cells. IL-2 signals through its heterotrimeric receptor (IL-2R) consisting of the CD25, CD122 and CD132 chains. CD25 knockout (KO) mice develop Sjögren Syndrome-like disease. This study investigates whether corneal CD25/IL-2 signaling is critical for ocular health.
METHODS: Eyes from C57BL/6 mice were collected and prepared for immunostaining or in-situ hybridization. Bulk RNA sequencing was performed on the corneal epithelium from wild-type and CD25KO mice. We generated a conditional corneal-specific deletion of CD25 in the corneal epithelium (CD25
RESULTS: In C57BL/6 mice, CD25 mRNA was expressed in ocular tissues. Protein expression of CD25, CD122, and CD132 was confirmed in the corneal epithelium. Delayed corneal re-epithelization was seen in female but not male CD25KO mice. There were 771 differentially expressed genes in the corneal epithelium of CD25KO compared to wild-type mice. While barrier function is disrupted in CD25
CONCLUSIONS: All three chains of the IL-2R are expressed in the corneal epithelium. Our results indicate for the first time, deleting CD25 systemically in all tissues in the mouse and deleting CD25 locally in just the corneal epithelium compromises corneal epithelial barrier function, leading to dry eye disease in female mice. Future studies are needed to delineate the pathways used by IL-2 signaling to influence cornea homeostasis.
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