IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model
IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model
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在类固醇不敏感的甲苯二异氰酸酯诱发的哮喘模型中，IL-17F（而不是 IL-17A）是气道炎症的基础
DOI：
10.1183/13993003.01510-2018
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发表时间：
2019-04-01
影响因子：
24.3
通讯作者：
Yao, Lihong
中科院分区：
文献类型：
--
作者：
Chen, Rongchang;Zhang, Qingling;Yao, Lihong
类固醇不敏感是哮喘治疗的主要问题。甲苯二异氰酸酯（TDI）是哮喘的主要过敏原之一，其诱导T辅助性Th 2和Th 17应答，并且通常与临床上对类固醇治疗的不良反应相关。我们试图评估吸入性和全身性类固醇对TDI诱导的哮喘模型的影响，并发现白细胞介素（IL）-17A和IL-17 F在该模型中的作用。将BALB/c小鼠暴露于TDI以产生哮喘模型，并用吸入丙酸氟替卡松、全身性泼尼松、抗IL-17 A、抗IL-17 F、重组IL-17 A或IL-17 F治疗。丙酸氟替卡松和泼尼松对TDI诱导的气道高反应性（AHR）、支气管嗜酸性粒细胞增多和嗜酸性粒细胞增多以及上皮杯状细胞化生均无影响。TDI诱导的Th 2和Th 17特征不受丙酸氟替卡松或泼尼松的抑制。TDI暴露后用抗IL-17 A治疗导致AHR增加，粘液产生加重和气道嗜酸性粒细胞募集，伴随Th 2应答增强，而抗IL-17 F改善TDI诱导的AHR和气道嗜酸性粒细胞增多，Th 17应答降低。重组IL-17 A和IL-17 F显示出与单克隆抗体相反的作用。IL-17 A和IL-17 F在TDI诱导的哮喘模型的气道炎症期间发挥不同的生物学作用，该模型对吸入和全身类固醇均无反应。在TDI诱导的类固醇不敏感的鼠哮喘模型中，IL-17 A通过抑制Th 2炎症和嗜酸性粒细胞募集来限制过敏反应，而IL-17 F通过驱动Th 17反应和嗜中性粒细胞浸润来调节气道炎症。http://ow.ly/vP2z30nk7Z3
Steroid insensitivity constitutes a major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both T-helper Th2 and Th17 responses, and is often associated with poor responsiveness to steroid treatment in the clinic. We sought to evaluate the effects of inhaled and systemic steroids on a TDI-induced asthma model and to find how interleukin (IL)-17A and IL-17F function in this model. BALB/c mice were exposed to TDI for generating an asthma model and were treated with inhaled fluticasone propionate, systemic prednisone, anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL-17F. Both fluticasone propionate and prednisone showed no effects on TDI-induced airway hyperresponsiveness (AHR), bronchial neutrophilia and eosinophilia, and epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by fluticasone propionate or prednisone. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses, whereas anti-IL-17F ameliorated TDI-induced AHR and airway neutrophilia, with decreased Th17 responses. Recombinant IL-17A and IL-17F showed opposite effects to the monoclonal antibodies. IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is unresponsive to both inhaled and systemic steroids. In a TDI-induced steroid-insensitive murine asthma model, IL-17A restricts allergic responses through suppressing Th2 inflammation and eosinophil recruitment, while IL-17F modulates airway inflammation by driving Th17 response and neutrophil infiltrates http://ow.ly/vP2z30nk7Z3