Evidence map›Paper›PMID 27077371›Full record

ArticlePloS one2016

Inhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression.

Jérémie D Goldstein, Aude Burlion, Bruno Zaragoza, Kélhia Sendeyo, Julia K Polansky, Jochen Huehn, Eliane Piaggio, Benoit L Salomon, Gilles Marodon

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

32 citing papers in PubMed, 48 citations in OpenAlex.

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  7. The 'TNature reviews. Rheumatology · 2025
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  8. Sex differences in disease: sex chromosome and immunity.Journal of translational medicine · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Jérémie D GoldsteinSorbonne Universités, UPMC Univ Paris 06, UMR-S CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, CNRS ERL 8255, Paris, France.
Aude BurlionSorbonne Universités, UPMC Univ Paris 06, UMR-S CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, CNRS ERL 8255, Paris, France.
Bruno ZaragozaSorbonne Universités, UPMC Univ Paris 06, UMR-S CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, CNRS ERL 8255, Paris, France.
Kélhia SendeyoSorbonne Universités, UPMC Univ Paris 06, UMR-S CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, CNRS ERL 8255, Paris, France.
Julia K PolanskyDepartment of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Jochen HuehnDepartment of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Eliane PiaggioINSERM U932, Institut Curie, Paris, France.
Benoit L SalomonSorbonne Universités, UPMC Univ Paris 06, UMR-S CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, CNRS ERL 8255, Paris, France.
Gilles MarodonSorbonne Universités, UPMC Univ Paris 06, UMR-S CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, CNRS ERL 8255, Paris, France.ORCID http://orcid.org/0000-0003-4889-6785
Centre National de la Recherche Scientifique · FRHelmholtz Centre for Infection Research · DEInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The IL-2/JAK3/STAT-5 signaling pathway is involved on the initiation and maintenance of the transcription factor Foxp3 in regulatory T cells (Treg) and has been associated with demethylation of the intronic Conserved Non Coding Sequence-2 (CNS2). However, the role of the JAK/STAT pathway in controlling Foxp3 in the short term has been poorly investigated. Using two different JAK/STAT pharmacological inhibitors, we observed a detectable loss of Foxp3 after 10 min. of treatment that affected 70% of the cells after one hour. Using cycloheximide, a general inhibitor of mRNA translation, we determined that Foxp3, but not CD25, has a high turnover in IL-2 stimulated Treg. This reduction was correlated with a rapid reduction of Foxp3 mRNA. This loss of Foxp3 was associated with a loss in STAT-5 binding to the CNS2, which however remains demethylated. Consequently, Foxp3 expression returns to normal level upon restoration of basal JAK/STAT signaling in vivo. Reduced expression of several genes defining Treg identity was also observed upon treatment. Thus, our results demonstrate that Foxp3 has a rapid turn over in Treg partly controlled at the transcriptional level by the JAK/STAT pathway.

Indexed as

AnimalsDNA MethylationForkhead Transcription FactorsGene Expression RegulationHumansIntronsJanus Kinase 3MiceProtein Kinase InhibitorsRNA, MessengerSignal TransductionSTAT5 Transcription FactorT-Lymphocytes, RegulatoryForkhead Transcription FactorsFOXP3 protein, humanFoxp3 protein, mouseJanus Kinase 3Protein Kinase InhibitorsRNA, MessengerSTAT5 Transcription Factor

Identifiers

PMID27077371
PMCPMC4831811
OpenAlexW2338752975

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.