Evidence map›Paper›PMID 26303210›Full record

ArticleImmunology and cell biology2015

TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes.

Divya Ramnath, Kathryn Tunny, Daniel M Hohenhaus, Claire M Pitts, Anne-Sophie Bergot, P Mark Hogarth, John A Hamilton, Ronan Kapetanovic, Richard A Sturm, Glen M Scholz and 1 more

Abstract read
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In one paragraph

Article in Immunology and cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

38 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Skin inflammatory cytokine gene expression in chronic whiplash-associated disorder: a cross-sectional study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Article
  3. Review
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  6. Association of partial infections with the risk of psoriasis: A two-sample Mendelian randomization study.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024
    Article
  7. Review
  8. Research progress on the neutrophil components and their interactions with immune cells in the development of psoriasis.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023
    Article
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  18. Article
  19. Article
  20. Interferon regulatory factor 6 is required for proper wound healing in vivo.Developmental dynamics : an official publication of the American Association of Anatomists · 2020
    Article
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

11 authors at 5 institutions in 1 country.

Divya RamnathInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Kathryn TunnyInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Daniel M HohenhausInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Claire M PittsInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Anne-Sophie BergotDiamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.
P Mark HogarthCentre for Immunology, Burnet Institute, Melbourne, Victoria, Australia.
John A HamiltonDepartment of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
Ronan KapetanovicInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Richard A SturmInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Glen M ScholzDepartment of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
Matthew J SweetInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
The University of Queensland · AUBurnet Institute · AUThe Royal Melbourne Hospital · AUThe University of Melbourne · AUTranslational Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interferon regulatory factor (IRF) family members impart cell-type specificity to toll-like receptor (TLR) signalling, and we recently identified a role for IRF6 in TLR2 signalling in epithelial cells. TLR3 has a well-characterized role in wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions in human keratinocytes. Primary keratinocytes responded robustly to the TLR3 agonist poly(IC) with upregulation of mRNAs for interferon-β (IFN-β), the interleukin-12 (IL-12) family member IL-23p19 and the chemokines IL-8 and chemokine (C-C motif) ligand 5 (CCL5). Silencing of IRF6 expression enhanced poly(IC)-inducible IFN-β mRNA levels and inhibited poly(IC)-inducible IL-23p19 mRNA expression in primary keratinocytes. Consistent with these data, co-transfection of IRF6 increased poly(IC)-inducible IL-23p19 promoter activity, but inhibited poly(IC)-inducible IFN-β promoter activity in reporter assays. Surprisingly, poly(IC) did not regulate IL-12p40 expression in keratinocytes, suggesting that TLR3-inducible IL-23p19 may have an IL-23-independent function in these cells. The only other IL-12 family member that was strongly poly(IC) inducible was EBI3, which has not been shown to heterodimerize with IL-23p19. Both co-immunoprecipitation and proximity ligation assays revealed that IL-23p19 and EBI3 interact in cells. Co-expression of IL-23p19 and EBI3, as compared with IL-23p19 alone, resulted in increased levels of secreted IL-23p19, implying a functional role for this heterodimer. In summary, we report that IRF6 regulates a subset of TLR3 responses in human keratinocytes, including the production of a novel IL-12 family heterodimer (p19/EBI3). We propose that the TLR3-IRF6-p19/EBI3 axis may regulate keratinocyte and/or immune cell functions in the context of cell damage and wound healing in the skin.

Indexed as

AnimalsCaco-2 CellsCell LineCell Line, TumorCells, CulturedGene ExpressionHEK293 CellsHeLa CellsHumansImmunoblottingInterferon Regulatory FactorsInterleukin-23 Subunit p19InterleukinsKeratinocytesMCF-7 CellsMicroscopy, ConfocalEBI3 protein, humanInterferon Regulatory FactorsInterleukin-23 Subunit p19InterleukinsIRF6 protein, humanMinor Histocompatibility AntigensPoly I-CToll-Like Receptor 3

Identifiers

PMID26303210
OpenAlexW1821541351

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.