糖皮质激素诱导的肿瘤坏死因子及其受体在支气管哮喘Tregs细胞免疫调节中的机制研究

在哮喘免疫学发病机制中，树突状细胞（DCs）抗原提呈状态及其对T细胞增殖分化和免疫应答的影响将直接决定哮喘的发生发展。研究证实哮喘患者存在调节性T细胞（Tregs）功能受抑制，增强Tregs免疫调节功能可恢复哮喘的免疫失衡，对哮喘起到保护作用。新近发现糖皮质激素诱导的肿瘤坏死因子及其受体（GITRL/GITR）参与了诸多免疫调控环节，抑制该通路可降低T细胞活化、增生，同时减弱Tregs的免疫调节功能。结合前期实验结果，我们认为该通路在哮喘免疫反应中起着重要作用。因此，本项目选择肺DCs为靶细胞，以GITRL/GITR通路为切入点，采用基因调控、转染等方法，从多环节调控该通路，初步探讨GITRL通路通过对DCs抗原提呈、Th亚群分化及调控Tregs功能的影响，进而起到哮喘保护作用，为哮喘的治疗提供新的思路。

In the immunology pathogenesis of asthma, the antigen presenting of dendritic cells (DCs) will affect T cell proliferation and differentiation and immune response, thus will directly determine the development of asthma. It is confirmed that regulatory T cells (Tregs) are inhibited in asthmatics, and enhancing the immunoregulatory function of Tregs can restore the immune imbalance, thus protect asthma. Glucocorticoid-induced tumor necrosis factor (GITR/GITRL) is involved in many immune regulatory processes. Inhibition of GITR/GITRL coupling can reduce T-cell activation and proliferation, thus inhibit the immunoregulatory function of Tregs. Based on our previous experimental results, we believe that GITR/GITRL coupling may play an important role in the immunoregulatory of asthma. Therefore, in this study, DCs are selected as the target cells, and GITR/GITRL pathway is chose as a key point, and gene silence and transfection are used to regulate this pathway from multiple aspects to investigate the effect of GITR/GITRL pathway on the antigen presentation of DCs, Th subpopulation differentiation and regulation of Tregs function, which may protect from asthma and provide a new idea for the treatment of asthma.