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
J Clin Invest.
2007;
117(10):2941–2951
doi:10.1172/JCI31546
This article Copyright © 2007, The American Society for Clinical Investigation
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D
evelopment 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.
