ArticleThe Journal of clinical investigation2012
The αvβ6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Increased density of intraepithelial mast cells in patients with exercise-induced bronchoconstriction regulated through epithelially derived thymic stromal lymphopoietin and IL-33.The Journal of allergy and clinical immunology · 2014Trial
- The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Mast Cell Chymase and Human Lung Fibroblast Interaction: Mechanisms and Implications for Asthma.Inflammation · 2026Article
- Intestinal mast cell-derived leukotrienes mediate the anaphylactic response to ingested antigens.Science (New York, N.Y.) · 2025Article
- Human intraepithelial mast cell differentiation and effector function are directed by TGF-β signaling.The Journal of clinical investigation · 2025Article
- Integrin α2β1 regulates collagen I tethering to modulate hyperresponsiveness in reactive airway disease models.The Journal of clinical investigation · 2021Article
- Lineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation.The Journal of experimental medicine · 2021Article
- The Art of Mast Cell Adhesion.Cells · 2020Review
- Review
- Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors.Journal of innate immunity · 2020Review
- Regulatory cytokine function in the respiratory tract.Mucosal immunology · 2019Review
- Mast Cells and Their Progenitors in Allergic Asthma.Frontiers in immunology · 2019Review
- Airway brushing as a new experimental methodology to detect airway gene expression signatures in mouse lung squamous cell carcinoma.Scientific reports · 2018Article
- Genome-Wide Gene Expression Changes in the Normal-Appearing Airway during the Evolution of Smoking-Associated Lung Adenocarcinoma.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?American journal of respiratory cell and molecular biology · 2017Review
- Targeting integrin α5β1 ameliorates severe airway hyperresponsiveness in experimental asthma.The Journal of clinical investigation · 2017Article
- Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma.The Journal of allergy and clinical immunology · 2017Article
- An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.PLoS pathogens · 2016Article
- Mast cell proteases as pharmacological targets.European journal of pharmacology · 2016Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Allergic asthma is the most common form of asthma, affecting more than 10 million Americans. Although it is clear that mast cells have a key role in the pathogenesis of allergic asthma, the mechanisms by which they regulate airway narrowing in vivo remain to be elucidated. Here we report that mice lacking αvβ6 integrin are protected from exaggerated airway narrowing in a model of allergic asthma. Expression microarrays of the airway epithelium revealed mast cell proteases among the most prominent differentially expressed genes, with expression of mouse mast cell protease 1 (mMCP-1) induced by allergen challenge in WT mice and expression of mMCP-4, -5, and -6 increased at baseline in β6-deficient mice. These findings were most likely explained by loss of TGF-β activation, since the epithelial integrin αvβ6 is a critical activator of latent TGF-β, and in vitro-differentiated mast cells showed TGF-β-dependent expression of mMCP-1 and suppression of mMCP-4 and -6. In vitro, mMCP-1 increased contractility of murine tracheal rings, an effect that depended on intact airway epithelium, whereas mMCP-4 inhibited IL-13-induced epithelial-independent enhancement of contractility. These results suggest that intraepithelial activation of TGF-β by the αvβ6 integrin regulates airway responsiveness by modulating mast cell protease expression and that these proteases and their proteolytic substrates could be novel targets for improved treatment of allergic asthma.
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Registered trials
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.