Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption

Authors

Anmar Abu-Romman, Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, United States. Electronic address: Anmar.Abu-Romman@bcm.edu.
Kaitlin K. Scholand, Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, United States; Department of Biosciences, Rice University, Houston, TX, United States. Electronic address: Kks7@bcm.edu.
Sonali Pal-Ghosh, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: spghosh@gwu.edu.
Zhiyuan Yu, Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, United States. Electronic address: zhiyuan.yu@bcm.edu.
Yashwawini Kelagere, Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, United States. Electronic address: yashaswinikelagere@gmail.com.
Ghasem Yazdanpanah, Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, United States. Electronic address: ghyazdan@uic.edu.
Winston W-Y Kao, Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, United States. Electronic address: kaoww@ucmail.uc.edu.
Vivien J. Coulson-Thomas, University of Houston, College of Optometry, Houston, TX, United States. Electronic address: vcoulsonthomas@gmail.com.
Mary Ann Stepp, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Department of Ophthalmology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: mastepp@gwu.edu.
Cintia S. de Paiva, Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, United States; Department of Biosciences, Rice University, Houston, TX, United States. Electronic address: cintiadp@bcm.edu.

Document Type

Journal Article

Publication Date

7-27-2023

Journal

The ocular surface

DOI

10.1016/j.jtos.2023.07.008

Keywords

CD25; Cornea; Corneal barrier; IL-2; Sex; Wound healing; dry eye

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). Corneal barrier function was evaluated based on the uptake of a fluorescent dye. Mice were subjected to unilateral corneal debridement, followed by epithelial closure over time. 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 mice, re-epithelialization rates are not delayed. 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.

APA Citation

Abu-Romman, Anmar; Scholand, Kaitlin K.; Pal-Ghosh, Sonali; Yu, Zhiyuan; Kelagere, Yashwawini; Yazdanpanah, Ghasem; Kao, Winston W-Y; Coulson-Thomas, Vivien J.; Stepp, Mary Ann; and de Paiva, Cintia S., "Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption" (2023). GW Authored Works. Paper 3015.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3015

Department

Anatomy and Regenerative Biology