Evidence map›Paper›PMID 37614946›Full record

ArticleFrontiers in medicine2023

Toll-like receptor 4 and Syk kinase shape dendritic cell-induced immune activation to major house dust mite allergens.

Stefanie Busold, Jaap H Akkerdaas, Esther M Zijlstra-Willems, Kees van der Graaf, Sander W Tas, Esther C de Jong, Ronald van Ree, Teunis B H Geijtenbeek

Open access · goldAbstract read
In one paragraph

Article in Frontiers in medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
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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 2 institutions in 1 country.

Stefanie BusoldAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Jaap H AkkerdaasAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Esther M Zijlstra-WillemsAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Kees van der GraafCiteq Biologics, Groningen, Netherlands.
Sander W TasAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Esther C de JongAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Ronald van ReeAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Teunis B H GeijtenbeekAmsterdam University Medical Centers, location AMC, Department of Experimental Immunology, Amsterdam, Netherlands.
Amsterdam University Medical Centers · NLUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: House dust mite (HDM) is a major cause of respiratory allergic diseases. Dendritic cells (DCs) play a central role in orchestrating adaptive allergic immune responses. However, it remains unclear how DCs become activated by HDM. Biochemical functions of the major HDM allergens Der p 1 (cysteine protease) and Der p 2 (MD2-mimick) have been implicated to contribute to DC activation. Methods: We investigated the immune activating potential of HDM extract and its major allergens Der p 1 and Der p 2 using monocyte-derived DCs (moDCs). Maturation and activation markers were monitored by flow cytometry and cytokine production by ELISA. Allergen depletion and proteinase K digestion were used to investigate the involvement of proteins, and in particular of the major allergens. Inhibitors of spleen tyrosine kinase (Syk), Toll-like receptor 4 (TLR4) and of C-type lectin receptors (CLRs) were used to identify the involved receptors. The contribution of endotoxins in moDC activation was assessed by their removal from HDM extract. Results: HDM extract induced DC maturation and cytokine responses in contrast to the natural purified major allergens Der p 1 and Der p 2. Proteinase K digestion and removal of Der p 1 or Der p 2 did not alter the immune stimulatory capacity of HDM extract. Antibodies against the CLRs Dectin-1, Dectin-2, and DC-SIGN did not affect cytokine responses. In contrast, Syk inhibition partially reduced IL-6, IL-12 and completely blocked IL-10. Blocking TLR4 signaling reduced the HDM-induced IL-10 and IL-12p70 induction, but not IL-6, while endotoxin removal potently abolished the induced cytokine response. Conclusion: Our data strongly suggest that HDM-induced DC activation is neither dependent on Der p 1 nor Der p 2, but depend on Syk and TLR4 activation, which might suggest a crosstalk between Syk and TLR4 pathways. Our data highlight that endotoxins play a potent role in immune responses targeting HDM.

Indexed as

dendritic cell activationDer p 1Der p 2house dust mite allergySykTLR4

Identifiers

PMID37614946
PMCPMC10442820
OpenAlexW4385658813

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.