Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France.
Artimmune SAS, 13 Avenue Buffon, Orléans 45100, France.
Clin Sci (Lond). 2017 Oct 12;131(20):2533-2548. doi: 10.1042/CS20171034. Print 2017 Oct 15.
T helper (Th)17 immune response participates in allergic lung inflammation and asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL-17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia, cytokine and chemokine production as found in absence of IL-17RA. Furthermore, specific antibody neutralization of either IL-17A or IL-17F given during the sensitization phase attenuated allergic lung inflammation and airway hyperreactivity. activation by HDM of primary dendritic cells revealed a comparable induction of CXCL1 and IL-6 expression and the response to IL-17A and IL-17F relied on IL-17RA signaling via the adaptor protein act1 in fibroblasts. Therefore, HDM-induced allergic respiratory response depends on IL-17RA via act1 signaling and inactivation of either IL-17A or IL-17F is sufficient to attenuate allergic asthma in mice.
辅助性 T 细胞 (Th)17 免疫反应参与过敏肺炎症，并且在缺乏白细胞介素 (IL)-17 的情况下，哮喘会减轻。由于 IL-17A 和 IL-17F 被诱导并结合共同受体 IL-17RA，我们想知道这两种细胞因子是否都有助于屋尘螨 (HDM) 诱导的哮喘。我们报告说，在缺乏 IL-17A 或 IL-17F 的情况下，过敏肺炎症减弱，气道高反应性、嗜酸性粒细胞炎症、杯状细胞增生、细胞因子和趋化因子产生减少，与缺乏 IL-17RA 的情况相同。此外，在致敏阶段给予 IL-17A 或 IL-17F 的特异性抗体中和也减轻了过敏肺炎症和气道高反应性。HDM 对原代树突状细胞的激活揭示了 CXCL1 和 IL-6 表达的可比诱导，并且对 IL-17A 和 IL-17F 的反应依赖于成纤维细胞中适配器蛋白 act1 的 IL-17RA 信号传导。因此，HDM 诱导的过敏呼吸道反应依赖于 IL-17RA 通过 act1 信号传导，并且失活 IL-17A 或 IL-17F 足以减轻小鼠的过敏性哮喘。
