Evidence map›Paper›PMID 25896227›Full record

ArticleJournal of leukocyte biology2015

Limited specificity of IRF3 and ISGF3 in the transcriptional innate-immune response to double-stranded RNA.

Diana R Ourthiague, Harry Birnbaum, Niklas Ortenlöf, Jesse D Vargas, Roy Wollman, Alexander Hoffmann

Abstract read
In one paragraph

Article in Journal of leukocyte biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

28 citing papers in PubMed, 34 citations in OpenAlex.

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  18. High Dose IFN-Frontiers in immunology · 2021
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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

6 authors at 3 institutions in 1 country.

Diana R Ourthiague*Signaling Systems Laboratory and Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA; and Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Harry Birnbaum*Signaling Systems Laboratory and Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA; and Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Niklas Ortenlöf*Signaling Systems Laboratory and Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA; and Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Jesse D Vargas*Signaling Systems Laboratory and Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA; and Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Roy Wollman*Signaling Systems Laboratory and Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA; and Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Alexander Hoffmann*Signaling Systems Laboratory and Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA; and Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA ahoffmann@ucla.edu.
University of California San Diego · USQB3 · USUniversity of California, Los Angeles · US

Funding

Regulation of signaling via the lkB-NF-kB interactionR01GM071573 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HOFFMANN, ALEXANDER · 2005 to 2013
$2.2M
The NF-kB signaling system as a regulator of B-cell activationR01AI083453 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HOFFMANN, ALEXANDER · 2010 to 2014
$1.7M
NIAID NIH HHS R01 AI083453NIGMS NIH HHS R01 GM071573
6 · The paper itself

Abstract

The innate immune response is largely initiated by pathogen-responsive activation of the transcription factor IRF3. Among other target genes, IRF3 controls the expression of IFN-β, which triggers the activation of the transcription factor ISGF3 via the IFNAR. IRF3 and ISGF3 have been reported to control many of the same target genes and together, control the antimicrobial innate-immune program; however, their respective contributions and specificities remain unclear. Here, we used genomic technologies to characterize their specificity in terms of their physical DNA-binding and genetic function. With the use of ChiP-seq and transcriptomic measurements in WT versus ifnar(-/-) versus ifnar(-/-)irf3(-/-) macrophages responding to intracellular dsRNA, we confirmed the known ISGF3 DNA-binding motif and further specified a distinct IRF3 consensus sequence. The functional specificity of IRF3 is particularly pronounced in cytokine/chemokine regulation; yet, even in the control of IFN-β, that specificity is not absolute. By mathematically modeling IFN-β production within an abstracted tissue layer, we find that IRF3 versus ISGF3 specificity may be critical to limiting IFN-β production and ISGF3 activation, temporally and spatially, but that partial overlap in their specificity is tolerable and may enhance the effectiveness of the innate-immune response.

Indexed as

AnimalsChromatin ImmunoprecipitationImmunity, InnateInterferon Regulatory Factor-3Interferon-Stimulated Gene Factor 3MiceMice, Inbred C57BLReverse Transcriptase Polymerase Chain ReactionRNA, Double-StrandedTranscription, GeneticInterferon Regulatory Factor-3Interferon-Stimulated Gene Factor 3Irf3 protein, mouseRNA, Double-Strandedfeed-forward loopgene expressioninterferonmathematical modelingpathogen response

Identifiers

PMID25896227
PMCPMC4467169
OpenAlexW2141806612

What OpenQuestion holds

Textmetadata
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.