Evidence map›Paper›PMID 23086448›Full record

ArticleNature immunology2012

The CD46-Jagged1 interaction is critical for human TH1 immunity.

Gaëlle Le Friec, Devon Sheppard, Pat Whiteman, Christian M Karsten, Salley Al-Tilib Shamoun, Adam Laing, Laurence Bugeon, Margaret J Dallman, Teresa Melchionna, Chandramouli Chillakuri and 11 more

Open access · greenAbstract read
In one paragraph

Article in Nature immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

120 citing papers in PubMed, 195 citations in OpenAlex.

  1. Trial
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  12. Article
  13. Inside job: Roles of intracellular C3.The Journal of allergy and clinical immunology · 2025
    Review
  14. Review
  15. Review
  16. Article
  17. The multiverse of CD46 and oncologic interactions.The Journal of clinical investigation · 2025
    Review
  18. Article
  19. Article
  20. Complement and T cell activation in transplantation.Transplantation reviews (Orlando, Fla.) · 2025
    Review

60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 9 institutions in 4 countries.

Gaëlle Le FriecDivision of Transplantation Immunology and Mucosal Biology, MRC Centre for Transplantation, King's College London, Guy's Hospital, London, UK.
Devon Sheppard
Pat Whiteman
Christian M Karsten
Salley Al-Tilib Shamoun
Adam Laing
Laurence Bugeon
Margaret J Dallman
Teresa Melchionna
Chandramouli Chillakuri
Richard A Smith
Christian Drouet
Lionel Couzi
Veronique Fremeaux-Bacchi
Jörg Köhl
Simon N Waddington
James M McDonnell
Alastair Baker
Penny A Handford
Susan M Lea
Claudia Kemper
Guy's Hospital · GBUniversity of Oxford · GBImperial College London · GBKings Health Partners · GBUniversity of Lübeck · DECentre Hospitalier Universitaire de Grenoble · FRHôpital Européen · FRKing's College London · GBUniversity College London · GB

Funding

Medical Research Council G1002165Medical Research Council MR/J006742/1Wellcome Trust 087928Wellcome Trust 097928/A/08/Z
6 · The paper itself

Abstract

CD46 is a complement regulator with important roles related to the immune response. CD46 functions as a pathogen receptor and is a potent costimulator for the induction of interferon-γ (IFN-γ)-secreting effector T helper type 1 (T(H)1) cells and their subsequent switch into interleukin 10 (IL-10)-producing regulatory T cells. Here we identified the Notch family member Jagged1 as a physiological ligand for CD46. Furthermore, we found that CD46 regulated the expression of Notch receptors and ligands during T cell activation and that disturbance of the CD46-Notch crosstalk impeded induction of IFN-γ and switching to IL-10. Notably, CD4(+) T cells from CD46-deficient patients and patients with hypomorphic mutations in the gene encoding Jagged1 (Alagille syndrome) failed to mount appropriate T(H)1 responses in vitro and in vivo, which suggested that CD46-Jagged1 crosstalk is responsible for the recurrent infections in subpopulations of these patients.

Indexed as

Lymphocyte ActivationAdultAlagille Syndromealpha CateninAnimalsCalcium-Binding ProteinsCells, CulturedChildChild, PreschoolHumansIntercellular Signaling Peptides and ProteinsInterferon-gammaInterleukin-10Jagged-1 ProteinMembrane Cofactor ProteinMembrane Proteinsalpha CateninCalcium-Binding ProteinsIntercellular Signaling Peptides and ProteinsInterferon-gammaInterleukin-10JAG1 protein, humanJag1 protein, mouseJagged-1 ProteinMembrane Cofactor ProteinMembrane ProteinsRNA, Small InterferingSerrate-Jagged Proteins

Identifiers

PMID23086448
PMCPMC3505834
OpenAlexW2079069090

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.