sGARP在全反式维甲酸诱导调节性T细胞辅助哮喘治疗中的作用研究

Bronchial asthma is a chronic disease that severely threatens public health all over the world. All-trans retinoic acid (ATRA) has been reported to be helpful in improving asthmatic airway inflammation. The preliminary study of this research team and literatures showed that its effects were related to the activation of regulatory T cells (Tregs), but its mechanism was not clear yet. Studies showed that glycoprotein A repetitive receptor (GARP) played a key role in the Tregs activation and the expression of key effector TGF-β1. Therefore, we put forward a hypothesis that ATRA participated in asthma immunotherapy through Tregs activation and its mechanism was related to its regulation for GARP. To prove this hypothesis, we firstly established the correlation between ATRA and pathological phenotype, immune function, number of Tregs and GARP level in the clinical samples of asthma patients with different ATRA levels of peripheral blood. Then, we verified the biological function of ATRA in regulating Tregs in in-vitro Tregs culture system as well as the effects on immune function.We also studied the functions of GARP. Finally, we established asthma animal model to determine the effects of ATRA in improving asthma phenotype through immunoregulation, intervene in the expression of GARP, and study its effects in this process. This study will be conducted to further clarify the immunopathology mechanism of asthma and find new therapeutic target so as to provide new ideas for the treatment of asthma.

支气管哮喘是全球范围内严重威胁公众健康的慢性疾病，维生素A活性代谢产物全反式维甲酸（ATRA）已被报道有助于改善哮喘气道炎症，结合本课题组前期研究及文献发现其作用与调节性T细胞（Tregs）的活化有关，但机制尚不清楚。研究表明糖蛋白A重复型受体（GARP）在Tregs活化和效应分子TGF-β1的表达中具有关键作用，由此我们假设：ATRA通过对Tregs的活化参与哮喘免疫治疗，其机制与其对GARP的调控有关。并设计以下试验：收集临床标本建立ATRA与哮喘患者病理表型、免疫功能、Tregs数量、GARP水平之间的相关性；体外试验验证ATRA调控Tregs的生物学功能并影响免疫功能，并研究GARP的作用；建立哮喘动物模型，确定ATRA通过免疫调节改善哮喘表型的作用，并干预GARP表达研究其在此过程中的作用。本课题将进一步阐明哮喘的免疫学发病机制，发现新的治疗靶点，为哮喘的治疗提供新的思路