IL-13R[alpha]2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice

• Published in: The Journal of clinical investigation Vol. 117; no. 10; p. 2941
• Main Authors: Wilson, Mark S, Elnekave, Eldad, Mentink-Kane, Margaret M, Hodges, Marcus G, Pesce, John T, Ramalingam, Thirumalai R, Thompson, Robert W, Kamanaka, Masahito, Flavell, Richard A, Keane-Myers, Andrea, Cheever, Allen W, Wynn, Thomas A
• Format: Journal Article
• Language: English
• Published: Ann Arbor American Society for Clinical Investigation 01-10-2007
• Subjects: Allergens; Allergies; Antigens; Asthma; Biomedical research; Cytokines; Infections; Inflammation; Lavage; Lungs; Pathology
• ISSN: 0021-9738; 1558-8238

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 alpha 2 (IL-13Ralpha2) 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-13Ralpha2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13Ralpha2-deficient mice illustrate an indispensable role for IL-13Ralpha2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Ralpha2 are both required to control chronic Th2-driven pathological responses.