| First Author | Lajoie S | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 10 | Pages | 928-35 |
| PubMed ID | 20802484 | Mgi Jnum | J:164688 |
| Mgi Id | MGI:4834967 | Doi | 10.1038/ni.1926 |
| Citation | Lajoie S, et al. (2010) Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol 11(10):928-35 |
| abstractText | 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. |
