Evidence map›Paper›PMID 19543397›Full record

ArticlePloS one2009

Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFbeta expression.

Timothy R D J Radstake, Lenny van Bon, Jasper Broen, Mark Wenink, Kim Santegoets, Yanhui Deng, Anila Hussaini, Robert Simms, William W Cruikshank, Robert Lafyatis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Risk variants disrupting enhancers of TProceedings of the National Academy of Sciences of the United States of America · 2019
    Trial
  4. Trial
  5. HLA-DRRespiratory research · 2026
    Article
  6. Transcriptional landscape of CD4+ T cells in Systemic Sclerosis.bioRxiv : the preprint server for biology · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Impaired Regulation by IL-35 in Systemic Sclerosis.International journal of molecular sciences · 2023
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. IL-33/Regulatory T-Cell Axis Suppresses Skin Fibrosis.The Journal of investigative dermatology · 2022
    Article
  17. Article
  18. Article
  19. Article
  20. Review

16 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

10 authors at 2 institutions in 2 countries.

Timothy R D J RadstakeDepartment of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. T.Radstake@reuma.umcn.nl
Lenny van Bon
Jasper Broen
Mark Wenink
Kim Santegoets
Yanhui Deng
Anila Hussaini
Robert Simms
William W Cruikshank
Robert Lafyatis
Boston University · USRadboud University Nijmegen · NL

Funding

Microarray biomarkers of disease activity and progression in systemic sclerosisU01AR055063 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LAFYATIS, ROBERT A. · 2007 to 2009
$639k
NIAMS NIH HHS U01 AR055063NIAMS NIH HHS U01AR055063
6 · The paper itself

Abstract

backgroundRegulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc). METHODS/PRINCIPAL

findingsPatients were subdivided as having limited cutaneous SSc (lcSSc, n = 20) or diffuse cutaneous SSc (dcSSc, n = 48). Further subdivision was made between early dcSSc (n = 24) and late dcSSc (n = 24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25(high)CD127(-) and CD4CD25(low)CD127(high) and CD3(+) cells. Suppressive function was correlated with CD69 surface expression and TGFbeta secretion/expression. The frequency of CD4(+)CD25(+) and CD25(high)FoxP3(high)CD127(neg) T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma. CONCLUSIONS/SIGNIFICANCE: These results indicate that soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFbeta expression. These data suggest that a defective Treg function may underlie the immune dysfunction in systemic sclerosis.

Indexed as

AdultAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, T-LymphocyteCase-Control StudiesCD3 ComplexCD69 AntigensFemaleHumansInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLectins, C-TypeLeukocytes, MononuclearMaleMiddle AgedScleroderma, SystemicAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, T-LymphocyteCD3 ComplexCD69 AntigensInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLectins, C-TypeTransforming Growth Factor beta

Identifiers

PMID19543397
PMCPMC2695559
OpenAlexW2080941879

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.