ArticleJournal of neuroinflammation2022
FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Evaluation of risk promoting effects for age-related macular degeneration by estradiol.PloS one · 2026Article
- Exploring the Immunomodulatory Role of Forkhead Box Protein 3 (FOXP3) in the Pathophysiology of Neuropsychiatric Disorders.Molecular neurobiology · 2025Review
- Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration.Journal of neuroinflammation · 2025Article
- Associations of the Adaptive Immune System and Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration.Frontiers in immunology · 2025Article
- Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Bioinformatics Analysis of Lactylation-related Biomarkers and Potential Pathogenesis Mechanisms in Age-related Macular Degeneration.Current genomics · 2025Article
- Spatial profiling of the mouse colonic immune landscape associated with colitis and sex.Communications biology · 2024Article
- Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium.Neurobiology of aging · 2024Article
- Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective.International journal of molecular sciences · 2023Review
- FOXP3 Isoforms Expression in Cervical Cancer: Evidence about the Cancer-Related Properties of FOXP3Δ2Δ7 in Keratinocytes.Cancers · 2023Article
- Adaptive immune crosstalk and complement dysregulation in the aging retina.Tzu chi medical journalReview
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundForkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive T cells into Tregs that can downregulate the effector function of other T cells. We previously detected the expression of FoxP3 in retinal pigment epithelial (RPE) cells, forming the outer blood-retina barrier of the immune privileged eye.
methodsWe investigated the expression, subcellular localization, and phosphorylation of FoxP3 in RPE cells in vivo and in vitro after treatment with various stressors including age, retinal laser burn, autoimmune inflammation, exposure to cigarette smoke, in addition of IL-1β and mechanical cell monolayer destruction. Eye tissue from humans, mouse models of retinal degeneration and rats, and ARPE-19, a human RPE cell line for in vitro experiments, underwent immunohistochemical, immunofluorescence staining, and PCR or immunoblot analysis to determine the intracellular localization and phosphorylation of FoxP3. Cytokine expression of stressed cultured RPE cells was investigated by multiplex bead analysis. Depletion of the FoxP3 gene was performed with CRISPR/Cas9 editing.
resultsRPE in vivo displayed increased nuclear FoxP3-expression with increases in age and inflammation, long-term exposure of mice to cigarette smoke, or after laser burn injury. The human RPE cell line ARPE-19 constitutively expressed nuclear FoxP3 under non-confluent culture conditions, representing a regulatory phenotype under chronic stress. Confluently grown cells expressed cytosolic FoxP3 that was translocated to the nucleus after treatment with IL-1β to imitate activated macrophages or after mechanical destruction of the monolayer. Moreover, with depletion of FoxP3, but not of a control gene, by CRISPR/Cas9 gene editing decreased stress resistance of RPE cells.
conclusionOur data suggest that FoxP3 is upregulated by age and under cellular stress and might be important for RPE function.
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