ArticleProceedings of the National Academy of Sciences of the United States of America2024
Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Immunometabolic regulation and tissue-resident immunity in autoimmune uveitis: from genetic susceptibility to the gut-spleen-eye axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of EGR2 and TGFB1 as Potential Immunoregulatory Biomarkers for Allergic Rhinitis: An Exploratory Bioinformatics and Pilot Validation Study.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- Article
- Genetic-Environmental Programming of Microglial Identity: Shaping Spatiotemporal Dynamics in Neurodevelopment and Neurodevelopmental Diseases.Cellular and molecular neurobiology · 2026Review
- TREM2 Regulates Microglial Activation via the ERK/p38 Signaling Pathway: Implications for the Pathogenesis of Experimental Autoimmune Uveitis.Investigative ophthalmology & visual science · 2026Article
- Article
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Cell death in uveitis: pyroptosis, ferroptosis, apoptosis, and beyond.Frontiers in immunology · 2026Review
- Elevated GDF15 in ocular fluids of patients with proliferative diabetic retinopathy.Frontiers in endocrinology · 2026Article
- Effect of Dipyridamole on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Pathogenicity.Investigative ophthalmology & visual science · 2025Article
- Inhibition of Egr2 Protects against TAC-induced Heart Failure in Mice by Suppressing Inflammation and Apoptosis Via Targeting Acot1 in Cardiomyocytes.Journal of cardiovascular translational research · 2025Article
- Muscone Attenuates Uveitis Through the PI3K/AKT Signaling Pathway.Investigative ophthalmology & visual science · 2025Article
- Review
- Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
14 authors.
Funding
Abstract
Uveitis is a vision-threatening disease primarily driven by a dysregulated immune response, with retinal microglia playing a pivotal role in its progression. Although the transcription factor EGR2 is known to be closely associated with uveitis, including Vogt-Koyanagi-Harada disease and Behcet's disease, and is essential for maintaining the dynamic homeostasis of autoimmunity, its exact role in uveitis remains unclear. In this study, diminished EGR2 expression was observed in both retinal microglia from experimental autoimmune uveitis (EAU) mice and inflammation-induced human microglia cell line (HMC3). We constructed a mice model with conditional knockout of EGR2 in microglia and found that EGR2 deficiency resulted in increased intraocular inflammation. Meanwhile, EGR2 overexpression downregulated the expression of inflammatory cytokines as well as cell migration and proliferation in HMC3 cells. Next, RNA sequencing and ChIP-PCR results indicated that EGR2 directly bound to its downstream target growth differentiation factor 15 (GDF15) and further regulated GDF15 transcription. Furthermore, intravitreal injection of GDF15 recombinant protein was shown to ameliorate EAU progression in vivo. Meanwhile, knockdown of GDF15 reversed the phenotype of EGR2 overexpression-induced microglial inflammation in vitro. In summary, this study highlighted the protective role of the transcription factor EGR2 in AU by modulating the microglial phenotype. GFD15 was identified as a downstream target of EGR2, providing a unique target for uveitis treatment.
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