Evidence map›Paper›PMID 37800478›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2024

α-Ketoglutarate-Dependent KDM6 Histone Demethylases and Interferon-Stimulated Gene Expression in Lupus.

Erica N Montano, Moumita Bose, Lihong Huo, Gantsetseg Tumurkhuu, Gabriela De Los Santos, Brianna Simental, Aleksandr B Stotland, Janet Wei, C Noel Bairey Merz, Jo Suda and 9 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
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  7. Tissue Immunometabolism in Autoimmunity.European journal of immunology · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review
  19. Article
  20. Review
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

19 authors at 1 institution in 1 country.

Erica N MontanoKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Moumita BoseKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Lihong HuoKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Gantsetseg TumurkhuuKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Gabriela De Los SantosKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Brianna SimentalKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Aleksandr B StotlandSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Janet WeiSmidt Heart Institute and Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
C Noel Bairey MerzSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0002-9933-5155
Jo SudaDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Gislaine MartinsCedars-Sinai Medical Center and F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, USA.
Sarfaraz LalaniWomen's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Kate LawrensonWomen's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yizhou WangDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Sarah ParkerSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Swamy VenuturupalliDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Mariko IshimoriDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Daniel J WallaceDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Caroline A JefferiesKao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0002-8879-6722
Cedars-Sinai Medical Center · US

Funding

Sex and gender differences in lupus - intersection between immunometabolism, epigenetic remodeling and cardiac involvementR01AI164504 · NIAID · CEDARS-SINAI MEDICAL CENTER · PI JEFFERIES, CAROLINE · 2021 to 2024
$2.3M
NIAID NIH HHS R01 AI164504NIH HHS R01-AI-164504
6 · The paper itself

Abstract

objectiveWe aimed to investigate the hypothesis that interferon (IFN)-stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes in metabolic reprogramming and epigenetic regulation of ISG expression.

methodsMonocytes from healthy volunteers and patients with SLE at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation, and gene expression. The histone demethylases KDM6A/B were inhibited using glycogen synthase kinase J4 (GSK-J4). GSK-J4 was tested in pristane and resiquimod (R848) models of IFN-driven SLE.

resultsSLE monocytes had enhanced rates of glycolysis and oxidative phosphorylation compared to healthy control monocytes, as well as increased levels of isocitrate dehydrogenase and its product, α-ketoglutarate (α-KG). Because α-KG is a required cofactor for histone demethylases KDM6A and KDM6B, we hypothesized that IFNα may be driving "trained immune" responses through altering histone methylation. IFNα priming (day 1) resulted in a sustained increase in the expression of ISGs in primed cells (day 5) and enhanced expression on restimulation with IFNα. Importantly, decreased H3K27 trimethylation was observed at the promoters of ISGs following IFNα priming. Finally, GSK-J4 (KDM6A/B inhibitor) resulted in decreased ISG expression in SLE patient monocytes, as well as reduced autoantibody production, ISG expression, and kidney pathology in R848-treated BALB/c mice.

conclusionOur study suggests long-term IFNα exposure alters the epigenetic regulation of ISG expression in SLE monocytes via changes in immunometabolism, a mechanism reflecting trained immunity to type I IFN. Importantly, it opens the possibility that targeting histone-modifying enzymes, such as KDM6A/B, may reduce IFN responses in SLE.

Indexed as

Interferon Type ILupus Erythematosus, SystemicAnimalsEpigenesis, GeneticGene ExpressionHistone DemethylasesHistonesHumansJumonji Domain-Containing Histone DemethylasesKetoglutaric AcidsMiceHistone DemethylasesHistonesInterferon Type IJumonji Domain-Containing Histone DemethylasesKDM6B protein, humanKetoglutaric Acids

Identifiers

PMID37800478
PMCPMC10922114
OpenAlexW4387392407

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.