Evidence map›Paper›PMID 26343373›Full record

ArticleOncotarget2015

Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP.

Eyad Elkord, May Abd Al Samid, Belal Chaudhary

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
5.3field-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

64 citing papers in PubMed, 88 citations in OpenAlex.

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4 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

3 authors at 3 institutions in 2 countries.

Eyad ElkordCollege of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
May Abd Al SamidCollege of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Belal ChaudharyBiomedical Research Centre, School of Environment & Life Sciences, University of Salford, Manchester, United Kingdom.
Cancer Research UK Manchester Institute · GBUnited Arab Emirates University · AEUniversity of Salford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3- T cells expressing Helios (FoxP3-Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/-Helios+). We show that CD4+GARP+/-LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios- Tregs upon TCR stimulation. Unlike FoxP3+Helios- Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.

Indexed as

CCAAT-Enhancer-Binding Protein-betaCells, CulturedForkhead Transcription FactorsHumansIkaros Transcription FactorInterleukin-10Lymphocyte ActivationMembrane ProteinsT-Lymphocytes, RegulatoryCCAAT-Enhancer-Binding Protein-betaForkhead Transcription FactorsFOXP3 protein, humanIkaros Transcription FactorIKZF2 protein, humanIL10 protein, humanInterleukin-10LRRC32 protein, humanMembrane ProteinsFoxP3GARP/LAPHeliosImmune responseImmunityImmunology and Microbiology Sectionregulatory T cells

Identifiers

PMID26343373
PMCPMC4652984
OpenAlexW1945928767

What OpenQuestion holds

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LicenceCC BY
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.