Evidence map›Paper›PMID 26774658›Full record

ArticleThe Journal of allergy and clinical immunology2016

IL-6 promotes an increase in human mast cell numbers and reactivity through suppression of suppressor of cytokine signaling 3.

Avanti Desai, Mi-Yeon Jung, Ana Olivera, Alasdair M Gilfillan, Calman Prussin, Arnold S Kirshenbaum, Michael A Beaven, Dean D Metcalfe

Open access · greenAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

65 citing papers in PubMed, 155 citations in OpenAlex.

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  10. Role of Mast Cells and Their Mediators in Chronic Kidney Diseases.International journal of molecular sciences · 2025
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  15. Fungal Head and Neck Dermatitis: Current Understanding and Management.Clinical reviews in allergy & immunology · 2024
    Review
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5 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

8 authors at 2 institutions in 1 country.

Avanti DesaiLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md. Electronic address: avanti.desai@nih.gov.
Mi-Yeon JungLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md.
Ana OliveraLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md.
Alasdair M GilfillanLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md.
Calman PrussinLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md.
Arnold S KirshenbaumLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md.
Michael A BeavenLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Dean D MetcalfeLaboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Md.
National Institute of Allergy and Infectious Diseases · USNational Institutes of Health · US

Funding

The Pathogenesis, Diagnosis, And Treatment Of Systemic Mast Cell DisordersZIAAI000249 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KOMAROW, HIRSH D · 2009 to 2025
$16.5M
Identification and Characterization of Signaling Pathways and Mediators Regulating Mast Cell-Related DisordersZIAAI001206 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI OLIVERA, ANA · 2015 to 2025
$11.3M
Integrated Signaling Pathways for the Enhancement of Mast Cell ActivationZIAAI000965 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI METCALFE, DEAN D · 2009 to 2018
$5.3M
Intramural NIH HHS ZIA AI000249
6 · The paper itself

Abstract

backgroundIL-6, levels of which are reported to be increased in association with mastocytosis, asthma, and urticaria, is used in conjunction with stem cell factor to generate CD34(+) cell-derived primary human mast cell (HuMC) cultures. Despite these associations, the effects on and mechanisms by which prolonged exposure to IL-6 alters HuMC numbers and function are not well understood.

objectivesWe sought to study the effect of IL-6 on HuMC function, the mechanisms by which IL-6 exerts its effects, and the relationship of these findings to mastocytosis.

methodsHuMCs were cultured in stem cell factor with or without IL-6. Responses to FcεRI aggregation and expression of proteases and receptors, including the soluble IL-6 receptor (sIL-6R), were then quantitated. Epigenetic changes in suppressor of cytokine signaling 3 (SOCS3) were determined by using methylation-specific PCR. Serum samples from healthy control subjects and patients with mastocytosis were assayed for IL-6, tryptase, and sIL-6R.

resultsIL-6 enhanced mast cell (MC) proliferation, maturation, and reactivity after FcεRI aggregation. IL-6 reduced expression of SOCS3, which correlated with methylation of the SOCS3 promoter and increased expression and activation of signal transducer and activator of transcription 3. IL-6 also suppressed constitutive production of sIL-6R, and serum levels of sIL-6R were similarly reduced in patients with mastocytosis.

conclusionIL-6 increases MC proliferation and formation of a more reactive phenotype enabled by suppressing proteolytic cleavage of sIL-6R from IL-6R and downregulation of the SOCS3 autoinhibitory pathway. We suggest IL-6 blockade might ameliorate MC-related symptoms and pathology in patients with MC-related diseases associated with increased IL-6 levels, including mastocytosis.

Indexed as

Cell CountCell ProliferationChymasesDNA MethylationHumansInterleukin-6Mast CellsPhosphorylationPromoter Regions, GeneticProtein BindingProto-Oncogene Proteins c-kitReceptors, IgEReceptors, Interleukin-6Signal TransductionSuppressor of Cytokine Signaling 3 ProteinChymasesInterleukin-6Proto-Oncogene Proteins c-kitReceptors, IgEReceptors, Interleukin-6Suppressor of Cytokine Signaling 3 ProteinIL-6Mast cellsmastocytosissignal transducer and activator of transcription 3stem cell factorsuppressor of cytokine signaling 3

Identifiers

PMID26774658
PMCPMC4899186
OpenAlexW2229494300

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.