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Citations to this article

The αvβ6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells
Kotaro Sugimoto, … , Xiaozhu Huang, Dean Sheppard
Kotaro Sugimoto, … , Xiaozhu Huang, Dean Sheppard
Published January 9, 2012
Citation Information: J Clin Invest. 2012;122(2):748-758. https://doi.org/10.1172/JCI58815.
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Research Article Inflammation Article has an altmetric score of 6

The αvβ6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells

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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.

Authors

Kotaro Sugimoto, Makoto Kudo, Aparna Sundaram, Xin Ren, Katherine Huang, Xin Bernstein, Yanli Wang, Wilfred W. Raymond, David J. Erle, Magnus Åbrink, George H. Caughey, Xiaozhu Huang, Dean Sheppard

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Total citations by year

Year: 2025 2024 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 1 1 1 4 3 2 2 4 5 6 4 5 38
Citation information
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Citations to this article in year 2020 (4)

Title and authors Publication Year
The ITGB6 gene: its role in experimental and clinical biology
A Meecham, JF Marshall
2020
Lineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation
T Derakhshan, SK Samuchiwal, N Hallen, LG Bankova, JA Boyce, NA Barrett, KF Austen, DF Dwyer
Journal of Experimental Medicine 2020
Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors
G Pejler
Journal of Innate Immunity 2020
The Art of Mast Cell Adhesion
J Pastwińska, P Żelechowska, A Walczak-Drzewiecka, E Brzezińska-Błaszczyk, J Dastych
Cells 2020

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