ArticleArthritis & rheumatology (Hoboken, N.J.)2021
Inositol-Requiring Enzyme 1α-Mediated Synthesis of Monounsaturated Fatty Acids as a Driver of B Cell Differentiation and Lupus-like Autoimmune Disease.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Mechanism of Modified Shenqi Pill in Treatment of Allergic Rhinitis Comorbid with Asthma Based on Proteomics.Chinese journal of integrative medicine · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Single-nucleus transcriptome profiling of wild boar and domestic pig intestines reveals the spatiotemporal dynamics of immunity and nutrient absorption.Science China. Life sciences · 2026Article
- UPLC-MS/MS-based metabolomics analysis identifies disease-associated metabolic signatures of B cells from patients with IgG4-RD.Frontiers in immunology · 2026Article
- Identification of immune signatures associated with both SARS-CoV-2 infection and lung transplantation.Cell reports. Medicine · 2025Article
- Targeting polyunsaturated fatty acids desaturase FADS1 inhibits renal cancer growth via ATF3-mediated ER stress response.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- The role of fatty acid metabolism on B cells and B cell-related autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Impact of immune cell metabolism on membranous nephropathy and prospective therapy.Communications biology · 2025Review
- Myricetin exposure reduces PC differentiation in vitro in primary human B cells.Molecular medicine (Cambridge, Mass.) · 2025Article
- Fatty acid metabolism-derived prognostic model for lung adenocarcinoma: unraveling the link to survival and immune response.Frontiers in immunology · 2025Article
- Immunocyte lipid metabolic reprogramming: a novel pathway for targeted intervention in autoimmune diseases.Frontiers in immunology · 2025Review
- Inhalation exposure to airborne PMAmerican journal of physiology. Cell physiology · 2025Article
- Oxysterols contribute to immune cell recruitment in SLE skin lesions.Arthritis research & therapy · 2024Article
- Epinephrine promotes breast cancer metastasis through a ubiquitin-specific peptidase 22-mediated lipolysis circuit.Science advances · 2024Article
- Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response.bioRxiv : the preprint server for biology · 2024Article
- Review
- Endoplasmic Reticulum Stress in Systemic Lupus Erythematosus and Lupus Nephritis: Potential Therapeutic Target.Journal of immunology research · 2023Review
- Endoplasmic Reticulum Stress, Oxidative Stress, and Rheumatic Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Lipid Metabolism: Immune Regulation and Therapeutic Prospectives in Systemic Lupus Erythematosus.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveTo explore the molecular mechanisms underlying dysregulation of lipid metabolism in the pathogenesis of systemic lupus erythematosus (SLE).
methodsB cells in peripheral blood from patients with SLE and healthy controls were stained with BODIPY dye for detection of lipids. Mice with targeted knockout of genes for B cell-specific inositol-requiring enzyme 1α (IRE-1α) and stearoyl-coenzyme A desaturase 1 (SCD-1) were used for studying the influence of the IRE-1α/SCD-1/SCD-2 pathway on B cell differentiation and autoantibody production. The preclinical efficacy of IRE-1α suppression as a treatment for lupus was tested in MRL.Fas
resultsIn cultures with mouse IRE-1α-null B cells, supplementation with monounsaturated fatty acids largely rescued differentiation of plasma cells from B cells, indicating that the compromised capacity of B cell differentiation in the absence of IRE-1α may be attributable to a defect in monounsaturated fatty acid synthesis. Moreover, activation with IRE-1α/X-box binding protein 1 (XBP-1) was required to facilitate B cell expression of SCD-1 and SCD-2, which are 2 critical enzymes that catalyze monounsaturated fatty acid synthesis. Mice with targeted Scd1 gene deletion displayed a phenotype that was similar to that of IRE-1α-deficient mice, with diminished B cell differentiation into plasma cells. Importantly, in B cells from patients with lupus, both IRE-1α expression and Xbp1 messenger RNA splicing were significantly increased, and this was positively correlated with the expression of both Scd1 and Scd2 as well as with the amount of B cell lipid deposition. In MRL.Fas
conclusionThe results of this study reveal a molecular link in the dysregulation of lipid metabolism in the pathogenesis of lupus, demonstrating that the IRE-1α/XBP-1 pathway controls plasma cell differentiation through SCD-1/SCD-2-mediated monounsaturated fatty acid synthesis. These findings provide a rationale for targeting IRE-1α and monounsaturated fatty acid synthesis in the treatment of patients with 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.