IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice
Open Access
- 1 October 2007
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 117 (10), 2941-2951
- https://doi.org/10.1172/jci31546
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.Keywords
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