ArticlePloS one2013
Reducing FLI1 levels in the MRL/lpr lupus mouse model impacts T cell function by modulating glycosphingolipid metabolism.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond.Frontiers in immunology · 2022Pooled it
- Gastrodin enhances the spleen immune function in erythroleukemia by regulating T-cell receptor signaling pathway.Medical oncology (Northwood, London, England) · 2026Article
- STUB1-mediated ubiquitination regulates Fli-1 stability and CD4⁺T cell activation during inflammation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases.Biomolecules · 2025Review
- Sialic acid in the regulation of blood cell production, differentiation and turnover.Immunology · 2024Review
- Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- A cellular overview of immunometabolism in systemic lupus erythematosus.Oxford open immunology · 2023Review
- The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease.The Journal of clinical investigation · 2022Article
- Dysregulation and chronicity of pathogenic T cell responses in the pre-diseased stage of lupus.Frontiers in immunology · 2022Review
- T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy.Nature reviews. Rheumatology · 2020Review
- Immunometabolism in the pathogenesis of systemic lupus erythematosus.Journal of translational autoimmunity · 2020Review
- T cell Metabolism in Lupus.Immunometabolism · 2020Article
- Targeting glycosphingolipid metabolism as a potential therapeutic approach for treating disease in female MRL/lpr lupus mice.PloS one · 2020Article
- Fli-1 transcription factor regulates the expression of caspase-1 in lung pericytes.Molecular immunology · 2019Article
- The Role of Glycosphingolipids in Immune Cell Functions.Frontiers in immunology · 2019Review
- Fli-1 Governs Pericyte Dysfunction in a Murine Model of Sepsis.The Journal of infectious diseases · 2018Article
- Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury.Journal of lipid research · 2017Article
- Fli-1, a Functional Factor Performed in Autoimmune Lupus.Inflammation · 2016Article
- Molecular signatures in systemic lupus erythematosus: distinction between disease flare and infection.Lupus science & medicine · 2016Article
- FLI1 Levels Impact CXCR3 Expression and Renal Infiltration of T Cells and Renal Glycosphingolipid Metabolism in the MRL/lpr Lupus Mouse Strain.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1(+/+) or Fli1(+/-) T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1(+/-) lupus T cells compared to animals receiving Fli1(+/+) lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1(+/-) T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1(+/+) T cells. Moreover, the Fli1(+/-) T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1(+/+) T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus.
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