Evidence map›Paper›PMID 23958647›Full record

ArticleThe Journal of allergy and clinical immunology2013

IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling.

Zhihong Chen, Shanze Wang, Nkiruka Erekosima, Yapeng Li, Jessie Hong, Xiaopeng Qi, Patricia Merkel, Vijaya Nagabhushanam, Eugene Choo, Rohit Katial and 7 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of allergy and clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 26 citations in OpenAlex.

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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

17 authors at 3 institutions in 2 countries.

Zhihong ChenDivision of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, Colo; Zhangshan Hospital, Fudan University, Shanghai, China.
Shanze Wang
Nkiruka Erekosima
Yapeng Li
Jessie Hong
Xiaopeng Qi
Patricia Merkel
Vijaya Nagabhushanam
Eugene Choo
Rohit Katial
Rafeul Alam
Anita Trikha
Hong Wei Chu
Yonghua Zhuang
Meiling Jin
Chunxue Bai
Hua Huang
University of Colorado Denver · USNational Jewish Health · USJinshan Hospital of Fudan University · CN

Funding

Role of MEK1 in T cell function in asthmaR01AI091614 · NIAID · NATIONAL JEWISH HEALTH · PI ALAM, RAFEUL · 2011 to 2015
$2.0M
Gene Responses in Basophil-Mediated Allergic ResponsesR01AI083986 · NIAID · NATIONAL JEWISH HEALTH · PI HUANG, HUA · 2010 to 2014
$1.9M
Coordinating Adaptive and Innate ImmunityR01AI068083 · NIAID · NATIONAL JEWISH HEALTH · PI HUANG, HUA · 2005 to 2010
$1.4M
NIAID NIH HHS AI068083 ARRANIAID NIH HHS R01 AI068083NIAID NIH HHS R01 AI083986NIAID NIH HHS R01AI083986NIAID NIH HHS R01 AI091614
6 · The paper itself

Abstract

backgroundTH2 cells play a critical role in the pathogenesis of allergic asthma. Established TH2 cells have been shown to resist reprogramming into TH1 cells. The inherent stability of TH2 cells poses a significant barrier to treating allergic diseases.

objectiveWe sought to understand the mechanisms by which CD4(+) T cells from asthmatic patients resist the IL-27-mediated inhibition.

methodsWe isolated and cultured CD4(+) T cells from both healthy subjects and allergic asthmatic patients to test whether IL-27 can inhibit IL-4 production by the cultured CD4(+) T cells using ELISA. Culturing conditions that resulted in resistance to IL-27 were determined by using both murine and human CD4(+) T-cell culture systems. Signal transducer and activator of transcription (STAT) 1 phosphorylation was analyzed by means of Western blotting and flow cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured by using quantitative PCR. The small interfering RNA method was used to knockdown the expression of Socs3 mRNA.

resultsWe demonstrated that CD4(+) T cells from asthmatic patients resisted the suppression of IL-4 production mediated by IL-27. We observed that repeated exposure to TH2-inducing conditions rendered healthy human CD4(+) T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. The knockdown of Socs3 mRNA expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated inhibition of IL-4 production.

conclusionsOur findings demonstrate that differentiated TH2 cells can resist IL-27-induced reprogramming toward TH1 cells by downregulating STAT1 phosphorylation and likely explain why the CD4(+) T cells of asthmatic patients are resistant to IL-27-mediated inhibition.

Indexed as

AnimalsAsthmaCD4-Positive T-LymphocytesCells, CulturedHumansHypersensitivity, ImmediateInterleukin-4InterleukinsMaleMiceMice, Inbred C57BLPhosphorylationReal-Time Polymerase Chain ReactionSignal TransductionSTAT1 Transcription FactorSuppressor of Cytokine Signaling ProteinsInterleukin-4InterleukinsMYDGF protein, humanSTAT1 protein, humanSTAT1 Transcription FactorSuppressor of Cytokine Signaling ProteinsAllophycocyaninAPCAsthmaHigh concentrations of T(H)2-inducing reagentsIL-27IL-27RIL-27 receptorIL-4Intermediate concentrations of T(H)2-inducing reagentsLow concentrations of T(H)2-inducing reagentsMean fluorescence intensityMemory non-T(H)2 cells, including T(H)1 and T(H)17 cellsMemory T(H)2 cellsMFINon-T(H)2(m)PEPhosphorylated STATPhycoerythrinpSTATqPCRQuantitative RT-PCRRecombinant humanRecombinant murinerhrmSignal transducer and activator of transcriptionsignal transducer and activator of transcription 1 signalingsiRNASmall interfering RNASOCSSTATSuppressor of cytokine signalingsuppressor of cytokine signaling 3T-betT-box transcription factorT(H)2(hi)T(H)2(int)T(H)2(lo)T(H)2(m)T(H)2 stability

Identifiers

PMID23958647
PMCPMC3788709
OpenAlexW1973961976

What OpenQuestion holds

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LicenceTDM
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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.