Abstract
Purpose :
Tight regulation of eye inflammation is essential to preventing local insult from impacting global homeostasis and impairing visual function. We have shown that immune cells with an immunoregulatory phenotype are recruited to the lens capsule surface in response to corneal wounding and Experimental Autoimmune Uveitis (EAU). While it is widely accepted that immunity is generated in a cell type- and stimulus-specific manner, whether a differential regulatory response by Lens Capsule Associated Immune Cells (LCA-ICs) exists between eye pathologies, remains unknown. Here, we investigated whether LCA-ICs responding to corneal erosion share a similar immunomodulatory signature to those recruited in EAU.
Methods :
Cornea debridement wounding was performed on BALB/c mice, and eyes were removed on day 28, when corneal erosions had formed. C57BL/6J mice were immunized with peptide 651-670 of the interphotoreceptor retinoid-binding protein and harvested at day 18, a time of active EAU. Eyes were fixed, sectioned, and co-immunolabeled for LY6G, LY6C, MPO, CD68, Arg1, IL10, CD3 in various combinations, and examined by confocal microscopy.
Results :
The leukocytes that become associated with the lens capsule during active inflammation of EAU expressed markers of putative anti-inflammatory, pro-resolution immune subsets such as Arg1+ M2 macrophages and FoxP3+ regulatory T cells. While leukocytes were recruited to all regions of the lens capsule during EAU, in response to corneal erosions immune cells populated only the anterior cornea-facing and equatorial lens capsule surfaces. Most LCA-ICs responding to corneal erosions were identified as LY6G+LY6C+MPO+, resembling a neutrophil phenotype. CD68+ macrophages were present at a much lower frequency than in EAU, and this subset did not express M2 markers such as Arg1. No CD3+ T cells were detected among the LCA-ICs in the context of corneal erosions. The polymorphonuclear LCA-ICs responding to corneal erosion and CD68+ LCA-ICs recruited in EAU expressed the anti-inflammatory cytokine IL10. These results suggest that LCA-ICs likely regulate eye inflammation through an IL10-mediated inhibitory mechanism.
Conclusions :
Inflammation affecting different eye compartments induces the recruitment of distinct immune cell types to the lens capsule, with IL10 being a potential common immunoregulatory feature.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.