Epithelial IL-2 receptor expression and its effects on corneal nerves

Abstract

Purpose : The IL-2 receptor (IL-2R) is composed of three different chains, α (CD25), β, and g. CD25 is the binding arm of the receptor and critical for IL-2 signaling. CD25 is expressed primarily on immune cells, but an epithelial expression of CD25 has been reported in epithelia, including the cornea. We showed that CD25 null mice develop a Sjögren-like Syndrome, with ocular alterations, including loss of intraepithelial corneal nerves and decreased corneal mechanosensitivity. However, the role of epithelial CD25/IL-2 signaling has not been thoroughly investigated.

Methods : Corneal epithelium from 14-week old female C57BL/6 mice were collected and subjected to real-time PCR. Tear washings were collected and assayed for IL-2 and IL-1β. Laser scanning confocal microscopy evaluated the expression of CD25 within the corneal epithelium in wild-type C57BL/6 mice. Tet-On Krt12^rtTA (Keratin 12-reverse tetracycline-trans-activator knock-in), tet-O-Cre, and CD25^flox lines were mated to create a conditional, doxycycline-inducible Krt12^rtTA/rtTA/tet-O-Cre/CD25^flox/flox ternary mouse line (hereafter named CD25^Δ/ΔCEpi ) where CD25 is ablated only in the corneal epithelium after administration of doxycycline in chow. Offspring of both sexes were subjected to a doxycycline diet for four weeks, and corneal sensitivity was measured with a Cochet-Bonnet esthesiometer at eight weeks of age.

Results : In wild-type mice, mRNA expression of CD25, IL-2Rβ, and IL-2Rg was present in the corneal epithelium. IL-2 was detected in tears of naïve mice, while IL-1β was below the level of detection. Confocal microscopy showed that CD25 immunoreactivity is present in the cell membrane of apical and subapical epithelial cells but not in basal cells or intraepithelial nerves. A significant decrease in corneal sensitivity was observed in the induced-CD25^Δ/ΔCEpi mice compared to doxycycline-fed binary littermates Cre^(-), non-induced CD25^Δ/ΔCEpi mice, and binary littermates Cre^(-) mice on a regular diet.

Conclusions : All three chains of the IL-2R are expressed in the corneal epithelium. IL-2 is present in tears, bathing the ocular surface. Our results indicate that CD25/IL-2 epithelial signaling is important for corneal nerve homeostasis. Future studies are needed to delineate the mechanisms of how IL-2 preserves corneal nerves.

This is a 2021 ARVO Annual Meeting abstract.