Evidence map›Paper›PMID 24477913›Full record

Trial reportJournal of immunology (Baltimore, Md. : 1950)2014

Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung.

Isabel Vega-Carrascal, David A Bergin, Oliver J McElvaney, Cormac McCarthy, Nessa Banville, Kerstin Pohl, Mitsuomi Hirashima, Vijay K Kuchroo, Emer P Reeves, Noel G McElvaney

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Galectin-9Aging cell · 2026
    Article
  4. Review
  5. The Challenges of Detecting Neutrophil CFTR.Journal of innate immunity · 2026
    Review
  6. Article
  7. Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. A human receptor occupancy assay to measure anti-PD-1 binding in patients with prior anti-PD-1.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2021
    Article
  18. Article
  19. Article
  20. 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

10 authors at 4 institutions in 3 countries.

Isabel Vega-CarrascalRespiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland;
David A Bergin
Oliver J McElvaney
Cormac McCarthy
Nessa Banville
Kerstin Pohl
Mitsuomi Hirashima
Vijay K Kuchroo
Emer P Reeves
Noel G McElvaney
Royal College of Surgeons in Ireland · IEBeaumont Hospital · IEBrigham and Women's Hospital · USKagawa University Hospital · JP

Funding

Role of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI David A. Hafler · 1996 to 2026
$51.7M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5M
T CELL RESPONSE TO MYELIN PROTEOLIPID PROTEINR01NS030843 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 1998 to 2019
$4.1M
NIAID NIH HHS P01 AI039671NIAID NIH HHS P01 AI056299NINDS NIH HHS R01 NS030843
6 · The paper itself

Abstract

The T cell Ig and mucin domain-containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment.

Indexed as

Cystic FibrosisFemaleGalectinsHepatitis A Virus Cellular Receptor 2HumansLipopolysaccharidesLungMaleMembrane ProteinsNeutrophilsPseudomonas aeruginosaSignal TransductionGalectinsHAVCR2 protein, humanHepatitis A Virus Cellular Receptor 2LGALS9 protein, humanLipopolysaccharidesMembrane Proteins

Identifiers

PMID24477913
PMCPMC4997615
OpenAlexW1903306669

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.