ArticleThe Journal of experimental medicine2011
Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02683863 (An Open Label Study of the Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers in Subjects With Secondary Progressive Multiple Sclerosis), which is not on this map. Cited by 179 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open Label Study of the Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers in Subjects With Secondary Progressive Multiple Sclerosis
Who cites it
179 citing papers in PubMed, 2 syntheses or guidelines pooled it, 348 citations in OpenAlex.
- Oral fumaric acid esters for psoriasis.The Cochrane database of systematic reviews · 2015Pooled it
- Dimethyl fumarate for multiple sclerosis.The Cochrane database of systematic reviews · 2015Pooled it
- Dimethyl fumarate is efficacious in severe plaque psoriasis : Post hoc analysis from the BRIDGE trial in Austria.Wiener klinische Wochenschrift · 2019Trial
- Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS.Journal of neuroinflammation · 2017Trial
- Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study.Neurology · 2015Trial
- Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study.Journal of neurology · 2014Trial
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Dual role of microglia in glaucoma: Regulation of neuroinflammation and neuroregeneration.Neural regeneration research · 2026Article
- Neuroprotection and immunomodulation after treatment with NeuroBoost and NeuroHeal following ventral root crush in mice.IBRO neuroscience reports · 2026Article
- Treatment approaches to patients with multiple sclerosis and coexisting psoriasis - A longitudinal multicenter observational cohort study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Observational
- Cutaneous Dendritic Cells: Structure, Function and Immune Role.Biomedicines · 2026Review
- Dimethyl fumarate as an immunomodulatory enhancer of adipose-derived mesenchymal stem cells: therapeutic implications.Cell and tissue banking · 2026Article
- From gluten to therapeutics: molecular mechanisms of celiac disease and emerging alternatives to the gluten-free diet.Frontiers in pharmacology · 2026Review
- Psoriasis.Nature reviews. Disease primers · 2025Review
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- The molecular subtypes of autoimmune diseases.Computational and structural biotechnology journal · 2024Review
- Immune cells mediate the effects of gut microbiota on neuropathic pain: a Mendelian randomization study.The journal of headache and pain · 2024Article
- Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosis.The Journal of clinical investigation · 2024Article
- Clinical implications for the association of psoriasis and multiple sclerosis: an observational study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Observational
119 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis. Type II DCs result from fumarate-induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-κB sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19. As a consequence, GSH depletion by small molecules such as fumarates induces type II DCs in mice and in humans that ameliorate inflammatory autoimmune diseases. This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.
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Registered trials
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.