ArticleJournal of neuroinflammation2024
Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Single-Cell RNA sequencing identifies NAMPT as a potential therapeutic target in autoimmune uveitis.Journal of advanced research · 2026Article
- Fumarate hydratase downregulation in myocardial tissue: a potential biomarker for death from mechanical asphyxia.Forensic science, medicine, and pathology · 2026Article
- Integrated omics reveal the effects of vitamin D deficiency on gut microbiota and plasma metabolism in experimental autoimmune uveitis.Journal of neuroinflammation · 2026Article
- Single-cell transcriptomic profiling reveals aberrant CD4⁺ naive T cell differentiation driving immune activation in Behçet's uveitis.Journal of translational medicine · 2025Article
- Effect of Dipyridamole on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Pathogenicity.Investigative ophthalmology & visual science · 2025Article
- The Advance of Single-Cell RNA Sequencing Applications in Ocular Physiology and Disease Research.Biomolecules · 2025Review
- NETs-CD44-IL-17A Feedback Loop Drives Th17-Mediated Inflammation in Behçet's Uveitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking.
methodsTo explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF.
resultsOur study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells.
conclusionsDMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.
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