Faculty, Staff and Student Publications

Language

English

Publication Date

12-19-2023

Journal

Proceedings of the National Academy of Sciences of the United States of America

DOI

10.1073/pnas.2311647120

PMID

38085785

PMCID

PMC10742376

PubMedCentral® Posted Date

12-12-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor on the RPE, subsequently triggering the production of interleukin-6. This cascade of cytokines initiated a metabolic reprogramming of subretinal microglia, enhancing their capacity for lipid metabolism. RPE-specific knockout of IL-17 receptor A led to the dysfunction of subretinal microglia and RPE pathology. Collectively, our findings suggest that responding to RPE injury, the choroidal γδ T cells can initiate a protective signaling cascade that ensures the proper functioning of subretinal microglia.

Keywords

Animals, Mice, Cytokines, Interleukin-17, Macular Degeneration, Retina, Retinal Degeneration, Retinal Pigment Epithelium, age-related macular degeneration, microglia, cytokine

Published Open-Access

yes

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