Evidence map›Paper›PMID 23273843›Full record

ArticleImmunity2013

The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response.

Mathieu Blanc, Wei Yuan Hsieh, Kevin A Robertson, Kai A Kropp, Thorsten Forster, Guanghou Shui, Paul Lacaze, Steven Watterson, Samantha J Griffiths, Nathanael J Spann and 13 more

Open access · hybridAbstract read
In one paragraph

Article in Immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.

0numbers the graph read from it
0cells of the map it votes in
245citing papers in PubMed
19.7field-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

245 citing papers in PubMed, 401 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Single-cell transcriptomics reveal alveolar macrophage-specific responses in single-hit ozone exposure model in mice.American journal of physiology. Lung cellular and molecular physiology · 2026
    Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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  20. Article

185 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 5 countries.

Mathieu BlancDivision of Pathway Medicine and Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK.
Wei Yuan Hsieh
Kevin A Robertson
Kai A Kropp
Thorsten Forster
Guanghou Shui
Paul Lacaze
Steven Watterson
Samantha J Griffiths
Nathanael J Spann
Anna Meljon
Simon Talbot
Kathiresan Krishnan
Douglas F Covey
Markus R Wenk
Marie Craigon
Zsolts Ruzsics
Jürgen Haas
Ana Angulo
William J Griffiths
Christopher K Glass
Yuqin Wang
Peter Ghazal
University of Edinburgh · GBSwansea University · GBNational University of Singapore · SGUniversity of California, San Diego · USWashington University in St. Louis · USConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESLudwig-Maximilians-Universität München · DE

Funding

Post-lysosomal cholesterol trafficking networksR01HL067773 · NHLBI · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 2002 to 2021
$6.3M
Biotechnology and Biological Sciences Research Council BB/C511356/1Biotechnology and Biological Sciences Research Council BB/C5113561Biotechnology and Biological Sciences Research Council BB/C515771/2Biotechnology and Biological Sciences Research Council BB/C5157712Biotechnology and Biological Sciences Research Council BB/D019621/1Biotechnology and Biological Sciences Research Council BB/H001018/1Biotechnology and Biological Sciences Research Council BB/H0010181Biotechnology and Biological Sciences Research Council BB/I0017351British Heart Foundation FS/05/022NHLBI NIH HHS HL67773NHLBI NIH HHS R01 HL067773Wellcome TrustWellcome Trust WT066784
6 · The paper itself

Abstract

Recent studies suggest that the sterol metabolic network participates in the interferon (IFN) antiviral response. However, the molecular mechanisms linking IFN with the sterol network and the identity of sterol mediators remain unknown. Here we report a cellular antiviral role for macrophage production of 25-hydroxycholesterol (cholest-5-en-3β,25-diol, 25HC) as a component of the sterol metabolic network linked to the IFN response via Stat1. By utilizing quantitative metabolome profiling of all naturally occurring oxysterols upon infection or IFN-stimulation, we reveal 25HC as the only macrophage-synthesized and -secreted oxysterol. We show that 25HC can act at multiple levels as a potent paracrine inhibitor of viral infection for a broad range of viruses. We also demonstrate, using transcriptional regulatory-network analyses, genetic interventions and chromatin immunoprecipitation experiments that Stat1 directly coupled Ch25h regulation to IFN in macrophages. Our studies describe a physiological role for 25HC as a sterol-lipid effector of an innate immune pathway.

Indexed as

AnimalsAntiviral AgentsBinding SitesBone Marrow CellsGene Expression RegulationHydroxycholesterolsInterferonsLiver X ReceptorsMacrophage ActivationMacrophagesMevalonic AcidMiceOrphan Nuclear ReceptorsPromoter Regions, GeneticProtein BindingSTAT1 Transcription Factor25-hydroxycholesterolAntiviral Agentscholesterol 25-hydroxylaseHydroxycholesterolsInterferonsLiver X ReceptorsMevalonic AcidOrphan Nuclear ReceptorsSTAT1 Transcription FactorSteroid Hydroxylases

Identifiers

PMID23273843
PMCPMC3556782
OpenAlexW2113504004

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.