Evidence map›Paper›PMID 36311787›Full record

ReviewFrontiers in immunology2022

Epithelial cell alarmin cytokines: Frontline mediators of the asthma inflammatory response.

Marc Duchesne, Isobel Okoye, Paige Lacy

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 2% 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

79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.

  1. Pooled it
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  6. Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026
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  8. Article
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  11. Tezepelumab Reduces Alarmin Cytokine Levels in Upper Airway Epithelial Cells in Patients With Severe Asthma.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026
    Article
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19 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Marc DuchesneAlberta Respiratory Centre, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Isobel OkoyeAlberta Respiratory Centre, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Paige LacyAlberta Respiratory Centre, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
University of Alberta · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The exposure of the airway epithelium to external stimuli such as allergens, microbes, and air pollution triggers the release of the alarmin cytokines IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). IL-25, IL-33 and TSLP interact with their ligands, IL-17RA, IL1RL1 and TSLPR respectively, expressed by hematopoietic and non-hematopoietic cells including dendritic cells, ILC2 cells, endothelial cells, and fibroblasts. Alarmins play key roles in driving type 2-high, and to a lesser extent type 2-low responses, in asthma. In addition, studies in which each of these three alarmins were targeted in allergen-challenged mice showed decreased chronicity of type-2 driven disease. Consequently, ascertaining the mechanism of activity of these upstream mediators has implications for understanding the outcome of targeted therapies designed to counteract their activity and alleviate downstream type 2-high and low effector responses. Furthermore, identifying the factors which shift the balance between the elicitation of type 2-high, eosinophilic asthma and type-2 low, neutrophilic-positive/negative asthma by alarmins is essential. In support of these efforts, observations from the NAVIGATOR trial imply that targeting TSLP in patients with tezepelumab results in reduced asthma exacerbations, improved lung function and control of the disease. In this review, we will discuss the mechanisms surrounding the secretion of IL-25, IL-33, and TSLP from the airway epithelium and how this influences the allergic airway cascade. We also review in detail how alarmin-receptor/co-receptor interactions modulate downstream allergic inflammation. Current strategies which target alarmins, their efficacy and inflammatory phenotype will be discussed.

Indexed as

AlarminsAsthmaAllergensAnimalsCytokinesEndothelial CellsEpithelial CellsImmunity, InnateInterleukin-1 Receptor-Like 1 ProteinInterleukin-33LymphocytesMiceAlarminsAllergensCytokinesIl1rl1 protein, mouseInterleukin-1 Receptor-Like 1 ProteinInterleukin-33allergyIL-25IL-33tezepelumabTSLP

Identifiers

PMID36311787
PMCPMC9616080
OpenAlexW4306178603

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.