Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Nat Immunol. 2010 Oct;11(10):928-35. doi: 10.1038/ni.1926. Epub 2010 Aug 29.
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.
严重哮喘与白细胞介素 17A（IL-17A）的产生有关。IL-17A 在严重哮喘中的确切作用及其产生的驱动因素尚不清楚。在这里，我们证明 IL-17A 通过增强 IL-13 驱动的反应，介导了易感小鼠的严重气道高反应性（AHR）。从机制上讲，我们证明 IL-17A 和 AHR 受到过敏原驱动的过敏毒素产生的调节，因为补体因子 5（C5）或补体受体 C5aR 缺失的小鼠表现出强烈的 IL-17A 反应，而 C3aR 缺失的小鼠在过敏原挑战后产生的 IL-17 产生辅助性 T 细胞（T(H)17 细胞）和 AHR 较少。C3a 和 C5a 的相反作用是通过它们对 IL-23 产生的相互调节来介导的。这些数据表明补体介导的 IL-23-T(H)17 轴的调节在严重哮喘中起关键作用。
