Evidence map›Paper›PMID 25820702›Full record

ArticleEuropean journal of immunology2015

Human tolerogenic dendritic cells produce IL-35 in the absence of other IL-12 family members.

Karen O Dixon, Sandra W van der Kooij, Dario A A Vignali, Cees van Kooten

Open access · bronzeAbstract read
In one paragraph

Article in European journal of immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.8field-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

56 citing papers in PubMed, 103 citations in OpenAlex.

  1. Article
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  4. Review
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  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Interleukin-35: Structure, Function and Its Impact on Immune-Related Diseases.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2021
    Review
  14. Article
  15. A myriad of roles of dendritic cells in atherosclerosis.Clinical and experimental immunology · 2021
    Review
  16. Tolerogenic Dendritic Cell-Based Approaches in Autoimmunity.International journal of molecular sciences · 2021
    Review
  17. Review
  18. CD3Frontiers in immunology · 2021
    Article
  19. Review
  20. IL-35: A Novel Immunomodulator in Hepatitis B Virus-Related Liver Diseases.Frontiers in cell and developmental biology · 2021
    Review
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

4 authors at 2 institutions in 2 countries.

Karen O DixonDepartment of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Sandra W van der KooijDepartment of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Dario A A VignaliDepartment of Immunology, University of Pittsburgh, PA, USA.
Cees van KootenDepartment of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NLUniversity of Pittsburgh · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
A Regulatory Triad: IL35, Tregs and iTr35R01AI091977 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VIGNALI, DARIO AA · 2011 to 2015
$2.0M
Interleukin-35 and the tumor microenvironmentR01CA203689 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VIGNALI, DARIO AA · 2016 to 2020
$1.9M
NCI NIH HHS CA21765NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA203689NIAID NIH HHS R01 AI091977
6 · The paper itself

Abstract

IL-35 is a cytokine of the IL-12 family, existing as a heterodimer of IL-12p35 and Ebi3. IL-35 has anti-inflammatory properties and is produced by regulatory T cells in humans and mice, where it is required for optimal suppression of immune responses. Distinct from other IL-12 cytokines, the expression of IL-35 has not been described in antigen-presenting cells. In view of the immune-regulatory properties of IL-35, we investigated the expression, regulation, and function of IL-12p35 and Ebi3 in human monocyte-derived dendritic cells and tolerogenic DCs (tolDCs). These tolDCs do not produce IL-12p70 or the homodimer IL-12p40. We demonstrate that tolDCs completely lack transcriptional expression of IL-12p40. However, tolDCs maintain mRNA expression of IL-12p35 and Ebi3. Using intracellular flow cytometry and Western blot analysis, we show that tolDCs produce Ebi3 and IL-12p35, and both can be enhanced upon stimulation with IFN-γ, LPS, or CD40L. tolDCs supernatants have the capacity to suppress T-cell activation. Using IL12A silencing, we demonstrate that IL-12p35 is required for tolDCs to reach their full suppressive potential. Taken together, our results indicate that tolDCs produce IL-35, providing an additional novel mechanism by which tolDCs elicit their tolerogenic potential.

Indexed as

Immune ToleranceAntigen-Presenting CellsB7-2 AntigenB7 AntigensB7-H1 AntigenDendritic CellsDexamethasoneGene ExpressionHumansInterleukin-12Interleukin-12 Subunit p35Interleukin-27InterleukinsLipopolysaccharidesMinor Histocompatibility AntigensPhenotypeB7-2 AntigenB7 AntigensB7-H1 AntigenDexamethasoneEBI3 protein, humanInterleukin-12Interleukin-12 Subunit p35Interleukin-27interleukin-35, humanInterleukinsLipopolysaccharidesMinor Histocompatibility AntigensDendritic cellsHumanIL-12/IL-35 axisTolerance

Identifiers

PMID25820702
PMCPMC4617619
OpenAlexW2068742874

What OpenQuestion holds

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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.