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- Title
Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma.
- Authors
Lajoie, Stephane; Lewkowich, Ian P; Suzuki, Yusuke; Clark, Jennifer R; Sproles, Alyssa A; Dienger, Krista; Budelsky, Alison L; Wills-Karp, Marsha
- Abstract
Severe asthma is associated with the production of interleukin 17A (IL-17A). The exact role of IL-17A in severe asthma and the factors that drive its production are unknown. Here we demonstrate that IL-17A mediated severe airway hyperresponsiveness (AHR) in susceptible strains of mice by enhancing IL-13-driven responses. Mechanistically, we demonstrate that IL-17A and AHR were regulated by allergen-driven production of anaphylatoxins, as mouse strains deficient in complement factor 5 (C5) or the complement receptor C5aR mounted robust IL-17A responses, whereas mice deficient in C3aR had fewer IL-17-producing helper T cells (T(H)17 cells) and less AHR after allergen challenge. The opposing effects of C3a and C5a were mediated through their reciprocal regulation of IL-23 production. These data demonstrate a critical role for complement-mediated regulation of the IL-23-T(H)17 axis in severe asthma.
- Publication
Nature immunology, 2010, Vol 11, Issue 10, p928
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1926