sPLA2-X及其信号通路在腺病毒载体携带结核抗原对支气管哮喘免疫保护中的作用及机制研究

Our previous results demonstrated that adenoviral vector harboring tuberculosis antigens induced balanced cellular immune response to inhibit the development of allergic asthma in mice,which the specific mechanism needs to be further elucidated.In view of the fact that sPLA2-X played an important role in the development of asthma,In this project, we will aim to investigate whether adenoviral vector harboring tuberculosis antigens plays an immune protective role by regulating sPLA2-X through the JNK/P38MAPK signaling pathway.we will evaluate whether adenoviral vector harboring tuberculosis antigens regulate the expression of sPLA2-X in mouse asthma model.then we sought to investigate the immunological protection against allergic asthma in mice after sPLA2-X gene and eosinophils deleted. Meanwhile, We will explore the impact of JNK/P38MAPK signaling pathway blockade or activation on the capacity of antigen-specific eosinophils proliferation and cytokine secretion will be addressed in vitro using mouse eosinophils isolated from lung, which will dissect the mechanism that adenoviral vector harboring tuberculosis antigens plays an immune protective role in allergic asthma in mice.This study will provide new insight and important therapeutic strategy for asthma treatment.

我们前期研究发现腺病毒载体携带结核抗原能产生均衡的细胞免疫反应，对哮喘模型产生很好的免疫保护作用，但具体机制需进一步阐明。鉴于sPLA2-X在哮喘发生发展中的重要作用，本研究旨在探讨腺病毒载体携带结核抗原是否通过调节sPLA2-X来发挥对哮喘的免疫保护作用，同时研究该作用是否与JNK/P38MAPK信号通路相关。我们在小鼠哮喘模型上评估腺病毒载体携带结核抗原是否调节sPLA2-X表达，并通过敲除sPLA2-X基因与删除嗜酸性粒细胞来观察腺病毒载体携带结核抗原对哮喘的免疫保护情况，同时通过sPLA2-X蛋白与结核抗原共同孵育小鼠嗜酸性粒细胞，分别阻断或激活JNK/P38MAPK信号通路，分析嗜酸性粒细胞的增殖能力及细胞因子分泌情况，从而阐明腺病毒载体携带结核抗原对哮喘模型的免疫保护与sPLA2-X及相关通路的关联。为哮喘治疗提供新的策略及思路。

我们前期研究发现腺病毒载体携带结核抗原对哮喘模型产生很好的免疫保护作用，鉴于sPLA2-X在哮喘发生发展中的重要作用，本研究旨在探讨腺病毒载体携带结核抗原是否通过调节sPLA2-X来发挥对哮喘的免疫保护作用，同时研究该作用是否与JNK/P38MAPK信号通路相关。结果已经证实sPLA2-X在腺病毒载体携带结核抗原抑制哮喘发作中起到的关键作用，腺病毒载体携带结核抗原（rAd5-gsgAM）可降低哮喘模型中sPLA2-X及其产物cPLA2、CysLT等表达,对哮喘模型的具有免疫保护情况。同时阐明腺病毒载体携带结核抗原与sPLA2-X及嗜酸性粒细胞之间的内在关联。阐明腺病毒载体携带结核抗原（rAd5-gsgAM）通过JNK/P38MAPK信号通路调节sPLA2-X及其产物、IL33/ST2，进而发挥抑制哮喘的作用。为哮喘治疗提供新的策略及思路。