Evidence map›Paper›PMID 17158224›Full record

ArticleBlood2007

Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor.

Matilde León-Ponte, Gerard P Ahern, Peta J O'Connell

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01650311 (Investigating Serotonin Signalling in IBD Patients), which is not on this map. Cited by 169 papers.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed
3.8field-weighted citation impact, top 8% 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.

NCT01650311 recruitingnot on this mapstarted 2012, after this paper: background citation

Investigating Serotonin Signalling in IBD Patients

TypeobservationalSponsorMcMaster UniversityRan2012 to 2026Enrolled60ConditionsInflammatory Bowel Disease
3 · Its place in the literature

Who cites it

169 citing papers in PubMed, 345 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Serotonin transporter SERT: a novel immune checkpoint for CD8Journal for immunotherapy of cancer · 2026
    Article
  11. Review
  12. Metabolic Checkpoints in CD8International journal of biological sciences · 2026
    Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. HAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  19. Review
  20. Review

109 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

3 authors at 3 institutions in 2 countries.

Matilde León-PonteRobarts Research Institute, 100 Perth Drive, London, Ontario, Canada.
Gerard P Ahern
Peta J O'Connell
Georgetown University · USRobarts Clinical Trials · CAWestern University · CA

Funding

Calcium Signaling in Dendritic Cell FunctionR01AI054450 · NIAID · GEORGETOWN UNIVERSITY · PI AHERN, GERARD P · 2003 to 2006
$1.1M
NIAID NIH HHS AI 054450NIAID NIH HHS R01 AI054450
6 · The paper itself

Abstract

Although typically considered a neurotransmitter, there is substantial evidence that serotonin (5-HT) plays an important role in the pathogenesis of inflammatory disorders. Despite these findings, the precise role of 5-HT in modulating immune function, particularly T-cell function, remains elusive. We report that naive T cells predominantly express the type 7 5-HT receptor (5-HTR), and expression of this protein is substantially enhanced on T-cell activation. In addition, T-cell activation leads to expression of the 5-HT(1B) and 5-HT(2A) receptors. Significantly, exogenous 5-HT induces rapid phosphorylation of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and IkappaBalpha in naive T cells. 5-HT-induced activation of ERK1/2 and NFkappaB is inhibited by preincubation with a specific 5-HT(7) receptor antagonist. Thus, 5-HT signaling via the 5-HT(7) receptor may contribute to early T-cell activation. In turn, 5-HT synthesized by T cells may act as an autocrine factor. Consistent with this hypothesis, we found that inhibition of 5-HT synthesis with parachlorophenylalanine (PCPA) impairs T-cell activation and proliferation. Combined, these data demonstrate a fundamental role for 5-HT as an intrinsic cofactor in T-cell activation and function and suggest an alternative mechanism through which immune function may be regulated by indoleamine 2,3-dioxygenase-mediated catabolism of tryptophan.

Indexed as

AnimalsAutocrine CommunicationCells, CulturedEnzyme ActivationFenclonineGene Expression RegulationI-kappa B ProteinsIndoleamine-Pyrrole 2,3,-DioxygenaseInflammationLymphocyte ActivationMaleMiceMice, Inbred BALB CMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NF-KappaB Inhibitor alphaFenclonineI-kappa B ProteinsIndoleamine-Pyrrole 2,3,-DioxygenaseMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NF-KappaB Inhibitor alphaNfkbia protein, mouseReceptor, Serotonin, 5-HT1BReceptors, SerotoninSerotoninserotonin 7 receptor

Identifiers

PMID17158224
PMCPMC1852236
OpenAlexW1983263255

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.