ArticleThe Journal of clinical investigation2014
Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 150 citations in OpenAlex.
- Trial
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- Article
- From Genes to Pathways: The Molecular Landscape of Systemic Lupus Erythematosus.International journal of molecular sciences · 2026Review
- Reduced late endosome/lysosome function promotes SLE through chronic PI3K activity and SHP-1/SHIP-1 defects.JCI insight · 2026Article
- In Vivo Accumulation of Regulatory T Cells Using Eliglustat-Loaded Cryogels.Advanced healthcare materials · 2025Article
- Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Taurine corrects lupus CD4Nutrition & metabolism · 2025Article
- Metabolomic analysis suggests thiamine monophosphate as a potential marker for mesenchymal stem cell transplantation outcomes in patients with SLE.Lupus science & medicine · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Immunocyte lipid metabolic reprogramming: a novel pathway for targeted intervention in autoimmune diseases.Frontiers in immunology · 2025Review
- Investigating Overlapping Genetic Factors and Novel Causal Genes in Autoimmune Diseases: A Transcriptome-Wide Association and Multiomics Study.International journal of genomics · 2025Article
- CD38 in SLE CD4 T cells promotes CaNature communications · 2024Article
- Metabolic alterations in vitamin D deficient systemic lupus erythematosus patients.Scientific reports · 2024Article
- Identification and experimental verification of immune-related hub genes in intervertebral disc degeneration.Heliyon · 2024Article
- Dysregulated lipid metabolism networks modulate T-cell function in people with relapsing-remitting multiple sclerosis.Clinical and experimental immunology · 2024Article
- Article
- Metabolic Modulators in Cardiovascular Complications of Systemic Lupus Erythematosus.Biomedicines · 2023Review
- Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft-associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor β (LXRβ), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.