Evidence map›Paper›PMID 21108475›Full record

ArticleEuropean journal of immunology2010

TLR-mediated signaling pathways circumvent the requirement for DAP12 in mast cells for the induction of inflammatory mediator release.

Daniel Smrz, Shoko Iwaki, Daniel W McVicar, Dean D Metcalfe, Alasdair M Gilfillan

Abstract read
In one paragraph

Article in European journal of immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Proteasome-driven modulation of immune and oxidative pathways during scorpion envenomation pathogenesis.The journal of venomous animals and toxins including tropical diseases · 2025
    Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Stem cell factor programs the mast cell activation phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2012
    Article
  11. Novel identified receptors on mast cells.Frontiers in immunology · 2012
    Article
  12. Article
  13. Article
  14. 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

5 authors at 3 institutions in 1 country.

Daniel SmrzLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA.
Shoko Iwaki
Daniel W McVicar
Dean D Metcalfe
Alasdair M Gilfillan
National Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USNational Cancer Institute · US

Funding

Signal Transduction of Paired Inhibitory Receptors of NK Cells and MacrophagesZIABC010300 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MCVICAR, DANIEL W. · 2009 to 2025
$24.6M
Integrated Signaling Pathways for the Enhancement of Mast Cell ActivationZIAAI000965 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI METCALFE, DEAN D · 2009 to 2018
$5.3M
Intramural NIH HHS ZIA AI000965
6 · The paper itself

Abstract

TLR, expressed on the surface of mast cells, respond to a variety of bacterial and viral components to induce and enhance high-affinity IgE receptor-mediated cytokine production. Recent reports have indicated that specific TLR-dependent responses in macrophages and dendritic cells are regulated by the ITAM-containing molecule, DAP12. When phosphorylated, DAP12 recruits Syk, which is a critical molecule for mast cell activation. We therefore examined whether DAP12 similarly regulates TLR-mediated responses in mast cells. DAP12 was confirmed to be expressed in both human and mouse mast cells and, upon phosphorylation, to recruit Syk. However, although TLR agonists induced cytokine production, and synergistically enhanced high-affinity IgE receptor-mediated cytokine production, surprisingly, they failed to increase DAP12 phosphorylation in mouse bone marrow-derived mast cells (BMMC). Furthermore, normal TLR-mediated responses were observed in DAP12(-/-) BMMC. However, DAP12 phosphorylation and subsequent Syk recruitment were observed in BMMC following Con A-induced aggregation of mannose-glycosylated receptors, and these responses, together with Con A-induced degranulation, were substantially reduced in the DAP12(-/-) BMMC. These data demonstrate that TLR have differential requirements for DAP12 for their function in different cell types and that the inability of TLR to influence mast cell degranulation may be linked to their inability to utilize DAP12 to recruit Syk.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBone MarrowCell DegranulationCells, CulturedConcanavalin AHumansInflammation MediatorsIntracellular Signaling Peptides and ProteinsMast CellsMembrane ProteinsMiceMice, KnockoutProtein-Tyrosine KinasesReceptor AggregationSignal TransductionAdaptor Proteins, Signal TransducingConcanavalin AInflammation MediatorsIntracellular Signaling Peptides and ProteinsMembrane ProteinsProtein-Tyrosine KinasesSyk KinaseSYK protein, humanSyk protein, mouseTYROBP protein, humanTyrobp protein, mouse

Identifiers

PMID21108475
PMCPMC3393881
OpenAlexW2039464438

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.