Immunoregulatory Properties of Immune Cells that Associate with the Lens Capsule Surface during Acute and Resolution Phases of Experimental Autoimmune Uveitis

Authors

Phuong M. Le, Thomas Jefferson UniversityFollow
Mary J. Mattapallil
Rachel R. Caspi
Mary Ann Stepp
A. Sue Menko, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

8-17-2024

Comments

This article is the author's final published version in American Journal of Pathology, Volume 194, Issue 11, November 2024, Pages 2194 - 2211.

The published version is available at https://doi.org/10.1016/j.ajpath.2024.07.021. Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc.

Abstract

Inflammation in the eye is tightly regulated to prevent vision impairment and irreversible blindness. Emerging evidence shows that immune cells are specifically recruited to the lens capsule in response to autoimmune uveitis, yet the potential that they have a role in regulating this inflammatory disease remained unexplored. Here, an immunolocalization approach combined with high-resolution confocal microscopy was used to investigate whether the immune cells that become stably associated with the lens capsule in the eyes of C57BL/6J mice with experimental autoimmune uveitis (EAU) have an immunoregulatory phenotype. These studies revealed that during the acute phase of uveitis, at day 18 after disease induction, the immune cells specifically recruited to the lens capsule, such as regulatory T cells [forkhead box P3 (FoxP3)+CD4+] and M2 macrophages (CD68+ arginase 1+IL-10+), included those with putative anti-inflammatory, proresolution roles. The frequency of these lens capsule–associated immunomodulatory phenotypes increased at day 35 after induction, during the resolution phase of EAU inflammation. At this later stage of resolution, most of the macrophages expressed CD206, a mannose receptor responsible for removing inflammatory molecules, in addition to arginase 1 and IL-10. These results suggest a previously unknown role for the lens as a site for recruitment of immune cells whose role is to suppress inflammation, promote resolution, and maintain remission of EAU.

Recommended Citation

Le, Phuong M.; Mattapallil, Mary J.; Caspi, Rachel R.; Stepp, Mary Ann; and Menko, A. Sue, "Immunoregulatory Properties of Immune Cells that Associate with the Lens Capsule Surface during Acute and Resolution Phases of Experimental Autoimmune Uveitis" (2024). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 426.
https://jdc.jefferson.edu/pacbfp/426

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

39159867

Language

English