Evidence map›Paper›PMID 35198887›Full record

ArticleiScience2022

Nrf2 activation reprograms macrophage intermediary metabolism and suppresses the type I interferon response.

Dylan G Ryan, Elena V Knatko, Alva M Casey, Jens L Hukelmann, Sharadha Dayalan Naidu, Alejandro J Brenes, Thanapon Ekkunagul, Christa Baker, Maureen Higgins, Laura Tronci and 11 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
8.1field-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

70 citing papers in PubMed, 101 citations in OpenAlex.

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  15. Food preservative tBHQ modulates Th17/TCurrent research in toxicology · 2026
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10 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

21 authors at 8 institutions in 3 countries.

Dylan G RyanSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Elena V KnatkoDivision of Cellular Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, James Arrott Drive, Dundee, Scotland, UK.
Alva M CaseyMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Jens L HukelmannDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Sharadha Dayalan NaiduDivision of Cellular Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, James Arrott Drive, Dundee, Scotland, UK.
Alejandro J BrenesDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Thanapon EkkunagulDivision of Cellular Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, James Arrott Drive, Dundee, Scotland, UK.
Christa BakerDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Maureen HigginsDivision of Cellular Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, James Arrott Drive, Dundee, Scotland, UK.
Laura TronciMedical Research Council Cancer Unit, University of Cambridge, Cambridge, UK.
Efterpi NikitopolouMedical Research Council Cancer Unit, University of Cambridge, Cambridge, UK.
Tadashi HondaDepartment of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, USA.
Richard C HartleySchool of Chemistry, University of Glasgow, Glasgow, UK.
Luke A J O'NeillSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Christian FrezzaMedical Research Council Cancer Unit, University of Cambridge, Cambridge, UK.
Angus I LamondCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Andrey Y AbramovDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
J Simon C ArthurDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Doreen A CantrellDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Michael P MurphyMedical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Albena T Dinkova-KostovaDivision of Cellular Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, James Arrott Drive, Dundee, Scotland, UK.
University of Dundee · GBUniversity of Cambridge · GBNinewells Hospital · GBMedical Research Council · GBNational Hospital for Neurology and Neurosurgery · GBStony Brook University · USTrinity College Dublin · IEUniversity of Glasgow · GB

Funding

Medical Research Council MC_UU_00015/3Medical Research Council MC_UU_12022/6Wellcome Trust 205023/Z/16/Z
6 · The paper itself

Abstract

To overcome oxidative, inflammatory, and metabolic stress, cells have evolved cytoprotective protein networks controlled by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and its negative regulator, Kelch-like ECH associated protein 1 (Keap1). Here, using high-resolution mass spectrometry we characterize the proteomes of macrophages with altered Nrf2 status revealing significant differences among the genotypes in metabolism and redox homeostasis, which were validated with respirometry and metabolomics. Nrf2 affected the proteome following lipopolysaccharide (LPS) stimulation, with alterations in redox, carbohydrate and lipid metabolism, and innate immunity. Notably, Nrf2 activation promoted mitochondrial fusion. The Keap1 inhibitor, 4-octyl itaconate remodeled the inflammatory macrophage proteome, increasing redox and suppressing type I interferon (IFN) response. Similarly, pharmacologic or genetic Nrf2 activation inhibited the transcription of IFN-β and its downstream effector IFIT2 during LPS stimulation. These data suggest that Nrf2 activation facilitates metabolic reprogramming and mitochondrial adaptation, and finetunes the innate immune response in macrophages.

Indexed as

BiochemistryImmunologyProteomics

Identifiers

PMID35198887
PMCPMC8844662
OpenAlexW4210673509

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.