Evidence map›Paper›PMID 24505473›Full record

ArticlePloS one2014

The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling.

Lisa Schreiber, Beate Pietzsch, Stefan Floess, Carla Farah, Lothar Jänsch, Ingo Schmitz, Jochen Huehn

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
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  10. CD4Frontiers in immunology · 2022
    Review
  11. Modulation of the Response toFrontiers in microbiology · 2022
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Heterogeneity and Stability in Foxp3+ Regulatory T Cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2017
    Review
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Lisa SchreiberDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Beate PietzschDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Stefan FloessDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Carla FarahDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Lothar JänschResearch Group Cellular Proteomics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Ingo SchmitzResearch Group Systems-oriented Immunology and Inflammation Research, Helmholtz Centre for Infection Research, Braunschweig, Germany ; Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany.
Jochen HuehnDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Helmholtz Centre for Infection Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regulatory T cells (Tregs) obtain immunosuppressive capacity by the upregulation of forkhead box protein 3 (Foxp3), and persistent expression of this transcription factor is required to maintain their immune regulatory function and ensure immune homeostasis. Stable Foxp3 expression is achieved through epigenetic modification of the Treg-specific demethylated region (TSDR), an evolutionarily conserved non-coding element within the Foxp3 gene locus. Here, we present molecular data suggesting that TSDR enhancer activity is restricted to T cells and cannot be induced in other immune cells such as macrophages or B cells. Since NF-κB signaling has been reported to be instrumental to induce Foxp3 expression during Treg development, we analyzed how NF-κB factors are involved in the molecular regulation of the TSDR. Unexpectedly, we neither observed transcriptional activity of a previously postulated NF-κB binding site within the TSDR nor did the entire TSDR show any transcriptional responsiveness to NF-κB activation at all. Finally, the NF-κB subunit c-Rel revealed to be dispensable for epigenetic imprinting of sustained Foxp3 expression by TSDR demethylation. In conclusion, we show that NF-κB signaling is not substantially involved in TSDR-mediated stabilization of Foxp3 expression in Tregs.

Indexed as

Gene Expression RegulationAnimalsCell Line, TumorDNA MethylationForkhead Transcription FactorsGenetic LociMiceMice, Inbred C57BLNF-kappa BSignal TransductionT-Lymphocytes, RegulatoryForkhead Transcription FactorsFoxp3 protein, mouseNF-kappa B

Identifiers

PMID24505473
PMCPMC3914969
OpenAlexW2041699717

What OpenQuestion holds

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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.