Evidence map›Paper›PMID 30158636›Full record

ArticleNature communications2018

Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming.

David Olagnier, Aske M Brandtoft, Camilla Gunderstofte, Nikolaj L Villadsen, Christian Krapp, Anne L Thielke, Anders Laustsen, Suraj Peri, Anne Louise Hansen, Lene Bonefeld and 24 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

179 citing papers in PubMed, 1 synthesis or guideline pooled it, 272 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  6. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  7. Article
  8. Article
  9. [Mechanisms of cGAS-STING signaling pathway mediated neuroinflammation in central nervous system and their therapeutic implications].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026
    Review
  10. Review
  11. Article
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119 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 7 institutions in 5 countries.

David OlagnierDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark. olagnier@biomed.au.dk.
Aske M BrandtoftDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-1086-0023
Camilla GunderstofteDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Nikolaj L VilladsenDepartment of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus, Denmark.
Christian KrappDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Anne L ThielkeDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Anders LaustsenDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Suraj PeriFox Chase Cancer Center, 333 Cottman Avenue, Philidelphia, PA, 19111-2497, USA.
Anne Louise HansenDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Lene BonefeldDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Jacob ThyrstedDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Victor BruunDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Marie B IversenDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Lin LinDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Virginia M ArtegoitiaDepartment of Food Science, Aarhus University, Kirstinebjergvej 10, 5792, Aarslev, Denmark.ORCID http://orcid.org/0000-0001-5469-8908
Chenhe SuLady Davis Institute-Jewish General Hospital, McGill University, Division of Experimental Medicine, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Long YangLady Davis Institute-Jewish General Hospital, McGill University, Division of Experimental Medicine, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Rongtuan LinLady Davis Institute-Jewish General Hospital, McGill University, Division of Experimental Medicine, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
Siddharth BalachandranFox Chase Cancer Center, 333 Cottman Avenue, Philidelphia, PA, 19111-2497, USA.
Yonglun LuoDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-0007-7759
Mette NyegaardDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-2967-6624
Bernadette MarreroTranslational Autoinflammatory Diseases Studies, NIAID, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Raphaela Goldbach-ManskyTranslational Autoinflammatory Diseases Studies, NIAID, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Mona MotwaniProgram in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Dylan G RyanSchool of biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, College Green, Dublin 2, D02 PN40, Ireland, UK.
Katherine A FitzgeraldProgram in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Luke A O'NeillSchool of biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, College Green, Dublin 2, D02 PN40, Ireland, UK.
Anne K HollensenDepartment of Molecular Biology and Genetics, Aarhus University, C.F. Moellers Allé 3, 8000, Aarhus, Denmark.
Christian K DamgaardDepartment of Molecular Biology and Genetics, Aarhus University, C.F. Moellers Allé 3, 8000, Aarhus, Denmark.
Frank V de PaoliDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.
Hanne C BertramDepartment of Food Science, Aarhus University, Kirstinebjergvej 10, 5792, Aarslev, Denmark.
Martin R JakobsenDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-8847-9201
Thomas B PoulsenDepartment of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus, Denmark.
Christian K HolmDepartment of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Bartholin Alle 6, 8000, Aarhus, Denmark. holm@biomed.au.dk.
Aarhus University · DKJewish General Hospital · CAFox Chase Cancer Center · USNational Institutes of Health · USTrinity College Dublin · IEUniversity of Massachusetts Chan Medical School · USBGI Group (China) · CN

Funding

Pathogenesis, and Outcome of Autoinflammatory Diseases, NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Stills-like Diseases, and other Undifferentiated Autoinflammatory DiseasesZIAAI001220 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GOLDBACH-MANSKY, RAPHAELA · 2017 to 2025
$22.3M
6 · The paper itself

Abstract

The transcription factor Nrf2 is a critical regulator of inflammatory responses. If and how Nrf2 also affects cytosolic nucleic acid sensing is currently unknown. Here we identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells. Here, Nrf2 activation decreases STING expression and responsiveness to STING agonists while increasing susceptibility to infection with DNA viruses. Mechanistically, Nrf2 regulates STING expression by decreasing STING mRNA stability. Repression of STING by Nrf2 occurs in metabolically reprogrammed cells following TLR4/7 engagement, and is inducible by a cell-permeable derivative of the TCA-cycle-derived metabolite itaconate (4-octyl-itaconate, 4-OI). Additionally, engagement of this pathway by 4-OI or the Nrf2 inducer sulforaphane is sufficient to repress STING expression and type I IFN production in cells from patients with STING-dependent interferonopathies. We propose Nrf2 inducers as a future treatment option in STING-dependent inflammatory diseases.

Indexed as

AnimalsCell Line, TumorCells, CulturedDNA VirusesGene ExpressionHumansInterferon Type ILeukocytes, MononuclearMembrane ProteinsMiceNF-E2-Related Factor 2RAW 264.7 CellsRNA, MessengerSTING ProteinSuccinatesInterferon Type Iitaconic acidMembrane ProteinsNF-E2-Related Factor 2RNA, MessengerSTING1 protein, humanSting1 protein, mouseSTING ProteinSuccinates

Identifiers

PMID30158636
PMCPMC6115435
OpenAlexW2888230285

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.