封闭胸腺基质淋巴生成素受体对超敏原引起的气道炎症性应答的作用(英文)

Effects of TSLPR blocking on allergen-induced airway inflammatory responses

目的为阐明胸腺基质淋巴生成素受体(Thymic stromal lymphopoietin receptor,TSLPR)在超敏原引起的气道炎症应答中的作用,并在小鼠模型中探讨局部封闭TSLPR用以缓解哮喘的可能性。方法对TSLPR抗体或同型抗体预处理,且以鸡卵白蛋白(OVA)诱导的各组小鼠,分别行气道浸润细胞的分类和记数、H&E和PAS的肺组织染色分析;并以酶联免疫吸附测定法(ELISA)检测支气管肺泡灌洗液中炎性细胞因子;进一步分析OVA激发的小鼠树突状细胞(DCs)的迁移能力和成熟状态。结果在小鼠OVA致敏前施以抗TSLPR抗体可显著减少气道粘液的分泌、嗜酸性粒细胞和淋巴细胞浸润;同时引发IL-4、IL-5水平的明显下降。而作为其机制之一,TSLPR的中和作用可阻止超敏原诱导的DCs的成熟和迁移。结论封闭TSLPR介导的信号通路可缓解哮喘小鼠的气道炎症反应,有望成为一项新的防治气道变应性疾病策略。

Objective To define the role of Thymic stromal lymphopoietin receptor （TSLPR） in allergen-primed airway inflammatory responses, and to investigate the possibility of alleviating allergic disorders by locally inhibiting TSLPR in an asthmatic mice model. Methods In the anti-TSLPR antibody or isotype-immunoglobulin pretreated, ovalbumin （OVA）- primed mice, the airway infiltrated cells were fractioned and counted, and histologic analysis of lung tissues was conducted by staining with hematoxylin and eosin （H＆E） and periodic acid sehiff （PAS） respectively. Also the levels of proinflammatory cytokines in bronchoalveolar lavage （BAL） were analyzed by ELISA. The effects of TSLPR inhibition on allergen-initiated responses were further evaluated by assessing the migratory ability and the maturation of OVA-induced dendritic cell （ DC）. Results Application of Anti-TSLPR antibody before OVA sensitization significantly decreased mucus production and infiltrated eosinophils and lymphocytes in asthmatic mice, together with a remarkable reduction of IL-4, IL- 5 levels in BAL. As a mechanism of this effect, neutralization of TSLPR inhibited the maturation and migration of DCs in response to allergen stimulation. Conclusion Blockade of TSLPR-mediated signaling alleviated the allergic airway inflammation, representing a novel strategy in treating airway atopic disorders.