ArticleArthritis & rheumatology (Hoboken, N.J.)2020
NF-E2-Related Factor 2 Regulates Interferon Receptor Expression and Alters Macrophage Polarization in Lupus.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2020. 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.
- Oxidative Stress and NRF2-Mediated Redox Regulation in Incomplete Systemic Lupus Erythematosus and Systemic Lupus Erythematosus.Antioxidants (Basel, Switzerland) · 2026Article
- Wounds and the Microbiota: The Healing Interplay Between Host and Microbial Communities.International journal of molecular sciences · 2025Review
- Oxidative stress responses inmBio · 2025Review
- Glutathione-ROS pathway activation by probiotic B240 augments macrophage response to influenza.Frontiers in cellular and infection microbiology · 2025Article
- Antibodies Against Anti-Oxidant Enzymes in Autoimmune Glomerulonephritis and in Antibody-Mediated Graft Rejection.Antioxidants (Basel, Switzerland) · 2024Article
- The Role of Antioxidant Transcription Factor Nrf2 and Its Activating Compounds in Systemic Lupus Erythematosus.Antioxidants (Basel, Switzerland) · 2024Review
- Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.Frontiers in immunology · 2024Article
- The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.The Journal of clinical investigation · 2023Article
- NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized Children.Pathogens (Basel, Switzerland) · 2023Article
- Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response.Molecules (Basel, Switzerland) · 2022Review
- The Potential of Nrf2 Activation as a Therapeutic Target in Systemic Lupus Erythematosus.Metabolites · 2022Review
- Oxidative Stress in SLE T Cells, Is NRF2 Really the Target to Treat?Frontiers in immunology · 2021Review
- Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
objectivePristane-induced lupus is associated with nonresolving inflammation and deficiency of proresolving macrophages. Proresolving nonclassic macrophages (NCMs) are less responsive to type I interferon (IFN) than classic macrophages (CMs; which are proinflammatory), reflecting their relative expression levels of the type I IFN receptor (IFNAR). This study was undertaken to investigate the regulation of IFNAR expression in macrophages.
methodsWe carried out gene expression profiling of purified CMs and NCMs from mice treated with pristane (which develop lupus) or mineral oil (non-lupus controls). Macrophage differentiation and IFNAR expression were examined in mice treated with NF-E2-related factor 2 (Nrf2) activators and inhibitors and in Nrf2-deficient mice. Nrf2 activity was also assessed in blood cells from patients with systemic lupus erythematosus (SLE). Significant differences were determined by Student's t-test.
resultsRNA sequencing revealed increased expression of genes regulated by the transcription factor Nrf2 in NCMs from mineral oil-treated versus pristane-treated mice and in NCMs versus CMs. The Nrf2 activator CDDO-imidazole (CDDO-Im) decreased CMs (P < 0.0001) and promoted the development of proresolving NCMs (P = 0.06), whereas the Nrf2 inhibitor brusatol increased CMs (P < 0.05) and decreased NCMs (P < 0.001). CDDO-Im decreased Ifnar1 (P < 0.001) and IFN-stimulated gene (ISG) expression in macrophages and alleviated oxidative stress (P < 0.05), whereas brusatol had the opposite effect (P < 0.01). Moreover, Ifnar1 and ISG expression levels were higher in Nrf2-knockout mice than controls (P < 0.05). As seen in mice with lupus, SLE patients showed evidence of low Nrf2 activity.
conclusionOur findings indicate that Nrf2 activation favors the resolution of chronic inflammation in lupus. Since autoantibody production and lupus nephritis depend on IFNAR signaling, the ability of Nrf2 activators to repolarize macrophages and reduce the INF signature suggests that these agents may warrant consideration for treating lupus.
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