Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma
Copyright policy )Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma
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.
- University System of Ohio United States
- Amgen (United States) United States
- Cincinnati Children's Hospital Medical Center United States
- University of Cincinnati United States
Male, Mice, Knockout, Anaphylatoxins, Mice, Inbred BALB C, Mice, Inbred C3H, Interleukin-13, Interleukin-17, Complement C5a, Allergens, Interleukin-23, Article, Asthma, Mice, Inbred C57BL, Mice, Mice, Inbred AKR, Mice, Inbred DBA, Complement C3a, Animals, Cytokines, Genetic Predisposition to Disease, Complement Activation
Male, Mice, Knockout, Anaphylatoxins, Mice, Inbred BALB C, Mice, Inbred C3H, Interleukin-13, Interleukin-17, Complement C5a, Allergens, Interleukin-23, Article, Asthma, Mice, Inbred C57BL, Mice, Mice, Inbred AKR, Mice, Inbred DBA, Complement C3a, Animals, Cytokines, Genetic Predisposition to Disease, Complement Activation
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