Evidence map›Paper›PMID 27421739›Full record

ArticleCytotherapy2016

In vitro cytokine licensing induces persistent permissive chromatin at the Indoleamine 2,3-dioxygenase promoter.

Yazmin I Rovira Gonzalez, Patrick J Lynch, Elaine E Thompson, Brian G Stultz, Deborah A Hursh

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

Article in Cytotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.0field-weighted citation impact, top 30% 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

20 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. NINJ1 impairs the anti-inflammatory function of hUC-MSCs with synergistic IFN-γ and TNF-α stimulation.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2025
    Article
  5. Article
  6. Persistent tailoring of MSC activation through genetic priming.Molecular therapy. Methods & clinical development · 2024
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. IFN-γ and TNF-α Pre-licensing Protects Mesenchymal Stromal Cells from the Pro-inflammatory Effects of Palmitate.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  19. Review
  20. Morphological features of IFN-γ-stimulated mesenchymal stromal cells predict overall immunosuppressive capacity.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
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

5 authors at 2 institutions in 1 country.

Yazmin I Rovira GonzalezCellular and Tissue Therapies Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Patrick J LynchCellular and Tissue Therapies Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: Patrick.Lynch@fda.hhs.gov.
Elaine E ThompsonCellular and Tissue Therapies Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Brian G StultzCellular and Tissue Therapies Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Deborah A HurshCellular and Tissue Therapies Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: Deborah.Hursh@fda.hhs.gov.
Center for Biologics Evaluation and Research · USUnited States Food and Drug Administration · US

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

backgroundMesenchymal stromal cells (MSCs) are being investigated as therapies for inflammatory diseases due to their immunosuppressive capacity. Interferon (IFN)-γ treatment primes MSC immunosuppression partially through induction of Indoleamine 2,3-dioxygenase (IDO1), which depletes tryptophan necessary to support proliferation of activated T cells. We investigated the role of histone modifications in the timing and maintenance of induced IDO1 expression in MSCs under clinical manufacturing conditions, such as cryopreservation.

methodsWe used chromatin immunoprecipitation and quantitative polymerase chain reaction (PCR) to assay levels of transcriptionally permissive acetylated H3K9 and repressive trimethylated H3K9 histone modifications surrounding the transcriptional start site for IDO1, and reverse transcriptase PCR and immunoblotting to detect messenger RNA (mRNA) and protein.

resultsMSCs derived from three donors approached maximum IDO1 mRNA levels following 24 hours of in vitro cytokine treatment. Induction of IDO1 expression correlated with increased acetylation of H3K9 concomitant with reduction of trimethylated H3K9 modifications at the promoter. Examination of two additional donors confirmed this result. While induced IDO1 levels decreased within 2 days after cytokine removal and freeze thawing, the activated chromatin state was maintained. Upon re-exposure to cytokines, previously primed MSCs accumulated near-maximum IDO1 mRNA levels within 4-8 h. DISCUSSION: Our data indicate that in vitro priming of MSCs causes chromatin remodeling at the IDO1 promoter, that this alteration is maintained during processing commonly used to prepare MSCs for clinical use and that, once primed, MSCs are poised for IDO1 expression even in the absence of cytokines.

Indexed as

AcetylationCells, CulturedChromatinChromatin Assembly and DisassemblyCryopreservationCytokinesGene Expression RegulationHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaLymphocyte ActivationMesenchymal Stem CellsPromoter Regions, GeneticRNA, MessengerTranscription Initiation SiteTumor Necrosis Factor-alphaChromatinCytokinesIDO1 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaRNA, MessengerTumor Necrosis Factor-alphachromatin remodelingcytokine licensinghistone modificationsimmunomodulationindoleamine 2,3-dioxygenasemesenchymal stromal cells

Identifiers

PMID27421739
PMCPMC4983509
OpenAlexW2466568865

What OpenQuestion holds

Textmetadata
LicenceTDM
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.