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Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma.

Authors: Lajoie, S  Lewkowich, IP  Suzuki, Y  Clark, JR  Sproles, AA  Dienger, K  Budelsky, AL  Wills-Karp, M 
Citation: Lajoie S, etal., Nat Immunol. 2010 Oct;11(10):928-35. Epub 2010 Aug 29.
Pubmed: (View Article at PubMed) PMID:20802484
DOI: Full-text: DOI:10.1038/ni.1926

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.

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CRRD Object Information
CRRD ID: 5129681
Created: 2011-04-05
Species: All species
Last Modified: 2011-04-05
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.