Evidence map›Paper›PMID 23203851›Full record

ArticleArthritis and rheumatism2013

Therapeutic efficacy of Tyro3, Axl, and Mer tyrosine kinase agonists in collagen-induced arthritis.

B T van den Brand, S Abdollahi-Roodsaz, E A Vermeij, M B Bennink, O J Arntz, C V Rothlin, W B van den Berg, F A J van de Loo

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

B T van den BrandRadboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
S Abdollahi-Roodsaz
E A Vermeij
M B Bennink
O J Arntz
C V Rothlin
W B van den Berg
F A J van de Loo
Radboud University Nijmegen · NLRadboud University Medical Center · NLYale University · US

Funding

TAM receptor tyrosine kinases in inflammatory boweldiseaseR01AI089824 · NIAID · YALE UNIVERSITY · PI ROTHLIN, CARLA · 2010 to 2018
$3.9M
NIAID NIH HHS R01 AI089824NIAID NIH HHS R01-AI-089824
6 · The paper itself

Abstract

objectiveHyperactivation of innate immunity by Toll-like receptors (TLRs) can contribute to the development of autoinflammatory or autoimmune diseases. This study evaluated the activation of Tyro3, Axl, Mer (TAM) receptors, physiologic negative regulators of TLRs, by their agonists, growth arrest-specific protein 6 (GAS-6) and protein S, in the prevention of collagen-induced arthritis (CIA).

methodsAdenoviruses overexpressing GAS-6 and protein S were injected intravenously or intraarticularly into mice during CIA. Splenic T helper cell subsets from intravenously injected mice were studied by flow cytometry, and the knee joints of mice injected intravenously and intraarticularly were assessed histologically. Synovium from mice injected intraarticularly was evaluated for cytokine and suppressor of cytokine signaling (SOCS) expression.

resultsProtein S significantly reduced ankle joint swelling when overexpressed systemically. Further analysis of knee joints revealed a moderate reduction in pathologic changes in the joint and a significant reduction in the number of splenic Th1 cells when protein S was overexpressed systemically. Local overexpression of GAS-6 decreased joint inflammation and joint pathology. Protein S treatment showed a similar trend of protection. Consistently, GAS-6 and protein S reduced cytokine production in the synovium. Moreover, levels of messenger RNA for interleukin-12 (IL-12) and IL-23 were reduced by GAS-6 and protein S treatment, with a corresponding decrease in the production of interferon-γ and IL-17. TAM ligand overexpression was associated with an increase in SOCS-3 levels, which likely contributed to the amelioration of arthritis.

conclusionThis study provides the first evidence that TAM receptor stimulation by GAS-6 and protein S can be used to ameliorate arthritis when applied systemically or locally. TAM receptor stimulation limits proinflammatory signaling and adaptive immunity. This pathway provides a novel strategy by which to combat rheumatoid arthritis.

Indexed as

AdenoviridaeAnimalsArthritis, ExperimentalAxl Receptor Tyrosine Kinasec-Mer Tyrosine KinaseCytokinesGenetic TherapyGrowth Arrest-Specific Protein 6Injections, Intra-ArticularIntercellular Signaling Peptides and ProteinsKnee JointMaleMiceMice, Inbred DBAProtein SProto-Oncogene ProteinsAxl Receptor Tyrosine Kinasec-Mer Tyrosine KinaseCytokinesGrowth Arrest-Specific Protein 6Intercellular Signaling Peptides and ProteinsMertk protein, mouseProtein SProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSocs3 protein, mouseSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTyro3 protein, mouse

Identifiers

PMID23203851
PMCPMC3582862
OpenAlexW2037655090

What OpenQuestion holds

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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.