调节性T 细胞(Treg)是控制Th细胞亚群分化的主要效应细胞，参与哮喘发病的调控。我们从海南红树林真菌中分离获得一种新结构活性物质Penicilazaphilone C (PAC)。前期研究发现，PAC能够减轻哮喘小鼠肺部的慢性炎症、逆转Th2/Th1免疫反应、调节Treg的功能。在此前期研究的基础上，我们将进一步建立传统OVA和反复感染合胞病毒二种哮喘模型，用PAC进行治疗并观察治疗效果和副作用。治疗结束时提取脾脏、淋巴结和肺组织分离Treg和其它免疫炎症细胞，采用流式细胞术和免疫学技术检测这些细胞的数量、表型和功能，了解这些细胞与Pc治疗效果之间的关系。最后，利用分子生物学、免疫学、细胞生物学等技术研究PAC通过调节Treg功能治疗哮喘的分子机理，为将PAC作为具有自主知识产权的治疗哮喘新型药物模型分子或先导结构奠定理论基础。本项目研究可能为哮喘提供新的治疗手段，具有良好的应前景。

Bronchial asthma is a common respiratory disease that is lack of specific therapeutic drugs in clinic and has became a challenge for research and various burdens to the asthmatic patients. At present, it is well known that Th2 immune response is the major mechanism that contributes to formation of the chronic inflammation of the asthmatic lunges, and that regulatory T cells are major regulator that can reverse the imbalance to the Th2/Th1 immune response. Penicilazaphilone C is a new azaphilone that was firstly isolated by our laboratory from a marine fungus Penicillium sclerotiorum growing in Hainan mangrove environment. Our initial study results showed that treatment of asthmatic model mice with Penicilazaphilone C significantly reduced airway inflammation and significantly decreased airway hyperresponsiveness. Moreover, Penicilazaphilone C treatment can also reversed Th2 to Th1 immune response and increased the number and function of regulatory T cells. These results indicate that Penicilazaphilone C is a potential chemical compound for asthma treatment. To further study the exact anti-asthma molecular mechanism of Penicilazaphilone C, in this study, we will establish conventional OVA-induced mouse asthma model and respiratory syncytial virus (RSV) repeatedly infection asthma model to further systematically study the anti-asthma effects and possible side effects induced by Penicilazaphilone C. In addition, in order to confirm the relationship between Penicilazaphilone C treatment and various immune cells (especially regulatory T cells), we will separate the regulatory T cells and other immune cell types from the spleen, lymphnodes and lung tissues and analyze their numbers, phenotypes and functions by flow cytometry and immunological methods. At last, we will use various methods, including molecular biology, immunology and cytobiology, to further study the molecular mechanisms related to why the regulatory T cells cause reversion of Th2 to Th1 immune response after Penicilazaphilone C treatment. Our study results will promote Penicilazaphilone C to be used as a potential anti-asthma drug in the future.