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β-Arrestin-2 regulates the development of allergic asthma
Julia K.L. Walker, … , David A. Schwartz, Robert J. Lefkowitz
Julia K.L. Walker, … , David A. Schwartz, Robert J. Lefkowitz
Published August 15, 2003
Citation Information: J Clin Invest. 2003;112(4):566-574. https://doi.org/10.1172/JCI17265.
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β-Arrestin-2 regulates the development of allergic asthma

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Abstract

Asthma is a chronic inflammatory disorder of the airways that is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. Migration of Th2 cells to the lung is key to their inflammatory function and is regulated in large part by chemokine receptors, members of the seven-membrane-spanning receptor family. It has been reported recently that T cells lacking β-arrestin-2, a G protein–coupled receptor regulatory protein, demonstrate impaired migration in vitro. Here we show that allergen-sensitized mice having a targeted deletion of the β-arrestin-2 gene do not accumulate T lymphocytes in their airways, nor do they demonstrate other physiological and inflammatory features characteristic of asthma. In contrast, the airway inflammatory response to LPS, an event not coordinated by Th2 cells, is fully functional in mice lacking β-arrestin-2. β-arrestin-2–deficient mice demonstrate OVA-specific IgE responses, but have defective macrophage-derived chemokine–mediated CD4+ T cell migration to the lung. This report provides the first evidence that β-arrestin-2 is required for the manifestation of allergic asthma. Because β-arrestin-2 regulates the development of allergic inflammation at a proximal step in the inflammatory cascade, novel therapies focused on this protein may prove useful in the treatment of asthma.

Authors

Julia K.L. Walker, Alan M. Fong, Barbara L. Lawson, Jordan D. Savov, Dhavalkumar D. Patel, David A. Schwartz, Robert J. Lefkowitz

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Figure 1

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Effect of OVA treatment on airway responsiveness. Airway responsiveness ...
Effect of OVA treatment on airway responsiveness. Airway responsiveness to methacholine, defined by the time-integrated change in peak airway pressure, or airway pressure time index (APTI), was measured for βarr2–/– (circles) and WT (squares) mice treated with either alum (filled symbols) or OVA (open symbols). Data are mean ± SEM; n = 9–12 mice per group. *Effect of OVA treatment was significantly different between WT and βarr2–/– mice. P < 0.05.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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