Evidence map›Paper›PMID 35931086›Full record

ArticleImmunity2022

DNA methyltransferase 3 alpha and TET methylcytosine dioxygenase 2 restrain mitochondrial DNA-mediated interferon signaling in macrophages.

Isidoro Cobo, Tiffany N Tanaka, Kailash Chandra Mangalhara, Addison Lana, Calvin Yeang, Claudia Han, Johannes Schlachetzki, Jean Challcombe, Bethany R Fixsen, Mashito Sakai and 9 more

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

Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Impact of CaInternational journal of molecular sciences · 2026
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 3 countries.

Isidoro CoboDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Tiffany N TanakaUniversity of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
Kailash Chandra MangalharaSalk Institute for Biological Studies, La Jolla, CA, USA.
Addison LanaDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Calvin YeangUniversity of California San Diego, Sulpizio Cardiovascular Center, La Jolla, CA, USA.
Claudia HanDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Johannes SchlachetzkiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Jean ChallcombeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Bethany R FixsenDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Mashito SakaiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.
Rick Z LiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Hannah FieldsUniversity of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
Michal MokryDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, 3584 EA Utrecht, the Netherlands.
Randy G TsaiUniversity of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
Rafael BejarUniversity of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
Koen PrangeDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
Menno de WintherDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
Gerald S ShadelSalk Institute for Biological Studies, La Jolla, CA, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: ckg@ucsd.edu.
University of California San Diego · USAmsterdam University Medical Centers · NLSalk Institute for Biological Studies · USNippon Medical School · JPWilhelmina Children's Hospital · NL

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
UC San Diego Clinical and Translational Research InstituteKL2TR001444 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEPP, COLIN A. · 2015 to 2024
$15.4M
Tissue-specific roles of FXR in CVD and NASHP01HL147835 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2020 to 2024
$12.2M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Mitochondrial DNA Stress Activation of Interferon Signaling and Lupus PathologyR01AR069876 · NIAMS · YALE UNIVERSITY · PI SHADEL, GERALD · 2017 to 2021
$2.1M
NCATS NIH HHS KL2 TR001444NHLBI NIH HHS P01 HL147835NIAMS NIH HHS R01 AR069876NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Deleterious somatic mutations in DNA methyltransferase 3 alpha (DNMT3A) and TET mehtylcytosine dioxygenase 2 (TET2) are associated with clonal expansion of hematopoietic cells and higher risk of cardiovascular disease (CVD). Here, we investigated roles of DNMT3A and TET2 in normal human monocyte-derived macrophages (MDM), in MDM isolated from individuals with DNMT3A or TET2 mutations, and in macrophages isolated from human atherosclerotic plaques. We found that loss of function of DNMT3A or TET2 resulted in a type I interferon response due to impaired mitochondrial DNA integrity and activation of cGAS signaling. DNMT3A and TET2 normally maintained mitochondrial DNA integrity by regulating the expression of transcription factor A mitochondria (TFAM) dependent on their interactions with RBPJ and ZNF143 at regulatory regions of the TFAM gene. These findings suggest that targeting the cGAS-type I IFN pathway may have therapeutic value in reducing risk of CVD in patients with DNMT3A or TET2 mutations.

Indexed as

Cardiovascular DiseasesDioxygenasesDNA-Binding ProteinsDNA Methyltransferase 3ADNA, MitochondrialHumansInterferonsMacrophagesMitochondriaMutationNucleotidyltransferasesProto-Oncogene ProteinsTrans-ActivatorsDioxygenasesDNA-Binding ProteinsDNA Methyltransferase 3ADNA, MitochondrialDNMT3A protein, humanInterferonsNucleotidyltransferasesProto-Oncogene ProteinsTET2 protein, humanTrans-ActivatorsZNF143 protein, humanatherosclerosisclonal hematopoiesisDNMT3Ainterferonmitochondria DNATET2TFAMtranscriptional regulation

Identifiers

PMID35931086
PMCPMC9718507
OpenAlexW4289794250

What OpenQuestion 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 OpenQuestion graph.