Evidence map›Paper›PMID 30199539›Full record

ArticlePLoS genetics2018

Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with susceptibility to inflammatory bowel disease.

Arianne C Richard, James E Peters, Natalia Savinykh, James C Lee, Eric T Hawley, Françoise Meylan, Richard M Siegel, Paul A Lyons, Kenneth G C Smith

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Gastroenterology report · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. A catalog of GWAS fine-mapping efforts in autoimmune disease.American journal of human genetics · 2021
    Review
  17. Article
  18. Article
  19. Role of Inflammation in Pathophysiology of Colonic Disease: An Update.International journal of molecular sciences · 2020
    Review
  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

9 authors at 2 institutions in 2 countries.

Arianne C RichardDepartment of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
James E PetersDepartment of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
Natalia SavinykhNIHR Cambridge BRC Cell Phenotyping Hub, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
James C LeeDepartment of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-5711-9385
Eric T HawleyImmunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States of America.ORCID 0000-0002-2357-2154
Françoise MeylanImmunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States of America.ORCID 0000-0002-9279-7875
Richard M SiegelImmunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States of America.
Paul A LyonsDepartment of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
Kenneth G C SmithDepartment of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
University of Cambridge · GBNational Institutes of Health · US

Funding

TNF-receptors and programmed cell death in regulation of autoimmunityZIAAR041133 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SIEGEL, RICHARD M · 2009 to 2019
$9.3M
British Heart Foundation RE/13/6/30180Medical Research Council MR/L019027/1Medical Research Council MR/L19027/1Wellcome TrustWellcome Trust 083650/Z/07/Z
6 · The paper itself

Abstract

Chronic inflammation in inflammatory bowel disease (IBD) results from a breakdown of intestinal immune homeostasis and compromise of the intestinal barrier. Genome-wide association studies have identified over 200 genetic loci associated with risk for IBD, but the functional mechanisms of most of these genetic variants remain unknown. Polymorphisms at the TNFSF15 locus, which encodes the TNF superfamily cytokine commonly known as TL1A, are associated with susceptibility to IBD in multiple ethnic groups. In a wide variety of murine models of inflammation including models of IBD, TNFSF15 promotes immunopathology by signaling through its receptor DR3. Such evidence has led to the hypothesis that expression of this lymphocyte costimulatory cytokine increases risk for IBD. In contrast, here we show that the IBD-risk haplotype at TNFSF15 is associated with decreased expression of the gene by peripheral blood monocytes in both healthy volunteers and IBD patients. This association persists under various stimulation conditions at both the RNA and protein levels and is maintained after macrophage differentiation. Utilizing a "recall-by-genotype" bioresource for allele-specific expression measurements in a functional fine-mapping assay, we localize the polymorphism controlling TNFSF15 expression to the regulatory region upstream of the gene. Through a T cell costimulation assay, we demonstrate that genetically regulated TNFSF15 has functional relevance. These findings indicate that genetically enhanced expression of TNFSF15 in specific cell types may confer protection against the development of IBD.

Indexed as

Genetic Predisposition to DiseaseAdultAllelesCells, CulturedColitis, UlcerativeCrohn DiseaseFemaleHaplotypesHumansMacrophagesMaleMiddle AgedMonocytesPolymorphism, Single NucleotidePrimary Cell CultureQuantitative Trait LociTNFSF15 protein, humanTumor Necrosis Factor Ligand Superfamily Member 15

Identifiers

PMID30199539
PMCPMC6130856
OpenAlexW2890502640

What OpenQuestion holds

Textmetadata
LicenceCC0
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.