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

Document Type

Journal Article

Publication Date

8-17-2024

Journal

The American journal of pathology

DOI

10.1016/j.ajpath.2024.07.021

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, using an immunolocalization approach combined with high-resolution confocal microscopy, we investigated 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 included those with putative anti-inflammatory, proresolution roles, such as regulatory T cells (FoxP3CD4) and M2 macrophages (CD68 arginase 1IL-10). 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. Our 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.

Department

Anatomy and Regenerative Biology

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