Ma Li, Xiao Xiaojun, Ma Yihe, Wu Haiqiang, Qiu Shuqi, Li Jing, Yang Pingchang, Liu Zhigang
The State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, School of Medicine, Shenzhen UniversityShenzhen 518116, China.
Shenzhen Key Laboratory of ENT, Institute of ENT & Longgang ENT HospitalShenzhen 518172, China.
Am J Transl Res. 2017 May 15;9(5):2143-2152. eCollection 2017.
Targeting Toll-like receptor 7 (TLR7) is known to have a potential therapeutic effect on experimental allergic asthma, but the exact mechanism is incompletely understood. To investigate the potential therapeutic effect of TLR7 agonist (TLR7a) a new versatile TLR7 agonist conjugated to Der f 1 was synthesized and evaluated here. It was confirmed that the course of airway hyperresponsiveness (AHR) and eosinophilia of the TLR7a vaccine-treated mice were limited. Levels of specific IgG1, IgG2a and IgE antibodies of these mice were changed obviously compared with that of the model mice. The expression of T helper 2 cytokine, interleukin (IL)-4, production in bronchoalveolar lavage fluid (BALF) and splenocytes were significantly decreased, while the levels of IFN-γ, IL-12 and IL-10 were increased after the treatment of TLR7a vaccine. In addition, Muc5 expression and goblet cells were significantly decreased in the lung tissue of asthma model mice treated with TLR7a plus Der f 1. These results suggest that the TLR7a-Der f 1 vaccine exhibits interesting therapeutic potency in suppressing allergic asthma and could be used a new agent in the treatment of allergic diseases.
已知靶向Toll样受体7(TLR7)对实验性变应性哮喘具有潜在治疗作用,但其确切机制尚不完全清楚。为了研究TLR7激动剂(TLR7a)的潜在治疗作用,本文合成并评估了一种与Der f 1偶联的新型通用TLR7激动剂。结果证实,经TLR7a疫苗治疗的小鼠气道高反应性(AHR)和嗜酸性粒细胞增多的病程受到限制。与模型小鼠相比,这些小鼠的特异性IgG1、IgG2a和IgE抗体水平发生了明显变化。经TLR7a疫苗治疗后,支气管肺泡灌洗液(BALF)和脾细胞中辅助性T细胞2细胞因子白细胞介素(IL)-4的表达和产生显著降低,而IFN-γ、IL-12和IL-10水平升高。此外,用TLR7a加Der f 1治疗的哮喘模型小鼠肺组织中Muc5表达和杯状细胞显著减少。这些结果表明,TLR7a-Der f 1疫苗在抑制变应性哮喘方面具有有趣的治疗潜力,可作为治疗变应性疾病的新型药物。