Evidence map›Paper›PMID 25609843›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

Positive feedback regulation of type I IFN production by the IFN-inducible DNA sensor cGAS.

Feng Ma, Bing Li, Su-yang Liu, Shankar S Iyer, Yongxin Yu, Aiping Wu, Genhong Cheng

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
4.7field-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

107 citing papers in PubMed, 162 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Amyloid-beta glycation induces neuronal mitochondrial dysfunction and Alzheimer's pathogenesis via VDAC1-dependent mtDNA efflux.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

47 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

7 authors at 2 institutions in 1 country.

Feng MaDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095;
Bing LiDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095; and.
Su-yang LiuDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095;
Shankar S IyerDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095;
Yongxin YuDivision of Oral Biology and Medicine, School of Dentistry and Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095.
Aiping WuDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095;
Genhong ChengDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095; gcheng@mednet.ucla.edu.
University of California, Los Angeles · USBroad Center · US

Funding

UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Vitamin D Metabolism in LeprosyP50AR063020 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2012 to 2016
$7.8M
Viral Mediated Type I Interferon InductionR01AI069120 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHENG, GENHONG · 2006 to 2021
$6.0M
Mechanisms of Biodefense By Toll-Like ReceptorsR01AI056154 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHENG, GENHONG · 2004 to 2014
$3.7M
Role of IRF3 and RXRa Crosstalk in Host Response to Viral InfectionsR01AI078389 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHENG, GENHONG · 2009 to 2013
$1.8M
NCI NIH HHS 5T32CA009120NCI NIH HHS T32 CA009120NIAID NIH HHS R01 AI056154NIAID NIH HHS R01 AI069120NIAID NIH HHS R01 AI078389NIAMS NIH HHS P50 AR063020
6 · The paper itself

Abstract

Rapid and robust induction of type I IFN (IFN-I) is a critical event in host antiviral innate immune response. It has been well demonstrated that cyclic GMP-AMP (cGAMP) synthase (cGAS) plays an important role in sensing cytosolic DNA and triggering STING dependent signaling to induce IFN-I. However, it is largely unknown how cGAS itself is regulated during pathogen infection and IFN-I production. In this study, we show that pattern recognition receptor (PRR) ligands, including lipid A, LPS, poly(I:C), poly(dA:dT), and cGAMP, induce cGAS expression in an IFN-I-dependent manner in both mouse and human macrophages. Further experiments indicated that cGAS is an IFN-stimulated gene (ISG), and two adjacent IFN-sensitive response elements (ISREs) in the promoter region of cGAS mediate the induction of cGAS by IFN-I. Additionally, we show that optimal production of IFN-β triggered by poly (dA:dT) or HSV-1 requires IFNAR signaling. Knockdown of the constitutively expressed DNA sensor DDX41 attenuates poly(dA:dT)-triggered IFN-β production and cGAS induction. By analyzing the dynamic expression of poly(dA:dT)-induced IFN-β and cGAS transcripts, we have found that induction of IFN-β is earlier than cGAS. Furthermore, we have provided evidence that induction of cGAS by IFN-I meditates the subsequent positive feedback regulation of DNA-triggered IFN-I production. Thus, our study not only provides a novel mechanism of modulating cGAS expression, but also adds another layer of regulation in DNA-triggered IFN-I production by induction of cGAS.

Indexed as

AnimalsCell LineChromatin ImmunoprecipitationCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseEnzyme-Linked Immunosorbent AssayFeedback, PhysiologicalHumansImmunity, InnateImmunoblottingInterferon Type IMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNucleotidyltransferasescGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon Type INucleotidyltransferases

Identifiers

PMID25609843
PMCPMC4324085
OpenAlexW1929156901

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.