ArticleJournal of immunology (Baltimore, Md. : 1950)2019
Dimethyl Fumarate Disrupts Human Innate Immune Signaling by Targeting the IRAK4-MyD88 Complex.
Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- NEK7 Cys298 is important for NLRP3 inflammasome and targetable by dimethyl fumarate.Cell chemical biology · 2026Article
- Dimethyl fumarate as a versatile therapeutic agent: molecular mechanisms and potential clinical applications.Molecular biology reports · 2026Review
- Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections.Archives of microbiology · 2026Review
- Proteome-wide ligandability maps of drugs with diverse cysteine-reactive chemotypes.Nature communications · 2025Article
- Dimethyl fumarate alleviate hepatic ischemia-reperfusion injury through suppressing cGAS-STING signaling.MedComm · 2025Article
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Metabolic Messengers: itaconate.Nature metabolism · 2024Review
- Disrupting pro-survival and inflammatory pathways with dimethyl fumarate sensitizes chronic lymphocytic leukemia to cell death.Cell death & disease · 2024Article
- Chemical immunology: Recent advances in tool development and applications.Cell chemical biology · 2024Review
- Review
- Antioxidant Dimethyl Fumarate Temporarily but Not Chronically Improves Intracortical Microelectrode Performance.Micromachines · 2023Article
- AzidoTMT Enables Direct Enrichment and Highly Multiplexed Quantitation of Proteome-Wide Functional Residues.Journal of proteome research · 2023Article
- Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon.Nature communications · 2023Article
- Identification of galectin-1 and other cellular targets of alpha,beta-unsaturated carbonyl compounds, including dimethylfumarate, by use of click-chemistry probes.Redox biology · 2023Article
- Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.Journal of neuroinflammation · 2022Review
- Advances in covalent drug discovery.Nature reviews. Drug discovery · 2022Review
- Blocking Caspase-1/Gsdmd and Caspase-3/-8/Gsdme pyroptotic pathways rescues silicosis in mice.PLoS genetics · 2022Article
- Innate immune signaling and immunothrombosis: New insights and therapeutic opportunities.European journal of immunology · 2022Review
- Small Molecules Targeting PTPσ-Trk Interactions Promote Sympathetic Nerve Regeneration.ACS chemical neuroscience · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Dimethyl fumarate (DMF) is a prescribed treatment for multiple sclerosis and has also been used to treat psoriasis. The electrophilicity of DMF suggests that its immunosuppressive activity is related to the covalent modification of cysteine residues in the human proteome. Nonetheless, our understanding of the proteins modified by DMF in human immune cells and the functional consequences of these reactions remains incomplete. In this study, we report that DMF inhibits human plasmacytoid dendritic cell function through a mechanism of action that is independent of the major electrophile sensor NRF2. Using chemical proteomics, we instead identify cysteine 13 of the innate immune kinase IRAK4 as a principal cellular target of DMF. We show that DMF blocks IRAK4-MyD88 interactions and IRAK4-mediated cytokine production in a cysteine 13-dependent manner. Our studies thus identify a proteomic hotspot for DMF action that constitutes a druggable protein-protein interface crucial for initiating innate immune responses.
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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.