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IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice
Mark S. Wilson, … , Allen W. Cheever, Thomas A. Wynn
Mark S. Wilson, … , Allen W. Cheever, Thomas A. Wynn
Published October 1, 2007
Citation Information: J Clin Invest. 2007;117(10):2941-2951. https://doi.org/10.1172/JCI31546.
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Research Article Immunology

IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice

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Abstract

Development of persistent Th2 responses in asthma and chronic helminth infections are a major health concern. IL-10 has been identified as a critical regulator of Th2 immunity, but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated pathology, with IL-10 deficiency resulting in increased Th2-driven inflammation but also reduced airway hyperreactivity (AHR), mucus hypersecretion, and fibrosis. We demonstrate that increased IL-13 receptor α 2 (IL-13Rα2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10–/– mice. Using models of allergic asthma and chronic helminth infection, we demonstrate that IL-10 and IL-13Rα2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13Rα2–deficient mice illustrate an indispensable role for IL-13Rα2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Rα2 are both required to control chronic Th2-driven pathological responses.

Authors

Mark S. Wilson, Eldad Elnekave, Margaret M. Mentink-Kane, Marcus G. Hodges, John T. Pesce, Thirumalai R. Ramalingam, Robert W. Thompson, Masahito Kamanaka, Richard A. Flavell, Andrea Keane-Myers, Allen W. Cheever, Thomas A. Wynn

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Figure 5

Removing IL-13Rα2 in IL-10–/– mice reveals a role for IL-13Rα2 in controlling AHR.

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Removing IL-13Rα2 in IL-10–/– mice reveals a role for IL-13Rα2 in contro...
Animals were sensitized and challenged as in Figure 1. Animals were euthanized 24 hours after the final airway challenge. (A) AHR. Penh measurements 24 hours after the final airway challenge using a Buxco system with mice exposed to increasing doses of methacholine. Results from 1 of 3 representative experiments are shown. (B) AHR. RL measurements 24 hours after the final airway challenge with mice exposed to increasing doses of methacholine. Results from 1 of 2 representative experiments are shown.

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