GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.

GITRL/GITR 信号通路在过敏、炎症、移植和自身免疫中发挥重要作用。然而，其在哮喘中的作用仍不清楚。因此，本研究旨在研究该途径的变化并观察其阻断对哮喘的治疗效果。采用屋尘螨诱发哮喘模型，观察GITRL/GITR及其下游分子MAPKs（如p38 MAPK、JNK和Erk）和NF-κB的变化。之后，用重组腺相关病毒敲低小鼠肺中的GITRL，观察对其下游分子的影响，评估对哮喘的治疗效果。这些结果表明 GITRL/GITR 及其下游分子 MAPKs/NF-κB 在哮喘小鼠中被激活。这种激活在 GITRL 击倒后被抑制，过敏性气道炎症和气道高反应性得到缓解。这些结果表明 GITRL/GITR-MAPKs/NF-κB 信号通路参与了哮喘的发病机制。阻断 GITRL/GITR 信号通路对屋尘螨诱发的过敏性哮喘小鼠模型具有保护作用。