Nuocyte细胞对小鼠气道变应性炎症的调控研究

The study is about the influence of Orai1 intervention in Nuocytes on reciprocity among Nuocytes,T cells and Th2 cells under allergic conditions of the mice upper and lower airway on the basis of our previous investigations. One of those investigations was about the promotion of Nuocytes cultured in vitro on the development of murine allergic rhinitis, and others were about the Orai1 channel functions in a murine allergic rhinitis model system. It is hypothesized by us that Nuocytes may induce the differentiation of na?ve T cells and may enhance the Th2 cells response in murine airway allergic state. Nuocytes are recently reported to play an important role in type II protective immunity to helminth parasites in an elegant study. However,it is not clear whether Nuocytes may contribute to acceleration and aggravation in the initiation and development of allergic inflammation which is a significant class of type II allergy. Thus we have designed the present study. Our research investigates the functions of Nuocytes in vivo and in vitro in the differentiation of na?ve T cells (into Th2 or Treg cell type) separated from the murine peripheral blood,and in the acceleration of Th2 cell response, and also assesses the regulation of Nuocytes functions by Th2 cells in allergic inflammation through immunofluorescence, western blot, enzyme-linked immunosorbent assay, real-time reverse transcription-polymerase chain reaction, cell culture,flow cytometry,lentivirus construction and transfection and laser scanning confocal microscope etc..Then the project explores the transformation of the differentiation of na?ve T cells into Th2 or Treg cell type and the reciprocity between Th2 cells and Nuocytes after the interfering of the Orai1 channel in the plasma membrane of Nuocytes simmilarly using the above experimental approaches plus patch clamp techniques.It may be concluded that Nuocytes play a crucial role in the initiation and development of the upper and lower airway allergic inflammation, and in vivo and in vitro facilitate the differentiation of na?ve T cells,and prompt the functions of Th2 cells and perform their corresponding activities under the control of Th2 cells. We may also conclude that the intervention of Orai1 channel of Nuocytes influences their various functions in allergic state in the murine airway mucosa and in the specific cultures. To sum up, this investigation is to be carried out in order to exploit new ideas and novel methods of going deeper into the study on allergic rhinitis and asthma,and is also to provide experiment data and theory basis on the pharmacal treatment of these two diseases.

本课题是建立在申请者前期关于Orai1通道研究成果和体外培养的Nuocyte细胞对小鼠气道模型的变应性炎症的促进作用的研究成果基础之上，以Nuocyte细胞在气道变应性炎症环境下可以诱导T细胞分化并可以放大Th2细胞效应为设想，拟研究Orai1通道干预对小鼠上、下气道变应性炎症环境下该细胞与T、Th2细胞间相互作用的影响。该研究以新近发现的在小鼠对抗寄生虫的II型免疫方面起重要作用的Nuocyte细胞为切入点，研究体内外Nuocyte细胞对初始T细胞分化的诱导作用（包括向Th2或Treg细胞亚类的分化），研究体内外该细胞对Th2细胞功能的促进作用，研究体内外Th2细胞对Nuocyte细胞功能的调控作用，并研究体内外Orai1通道干预对该细胞上述功能的影响。此项目旨在为变应性鼻炎和哮喘的研究开拓新思路，探索新方法，也为开发针对这类疾病的治疗药物提供实验根据和理论基础。

本课题是建立在申请者前期关于Orai1通道研究成果和体外培养的Nuocyte细胞对小鼠气道模型的变应性炎症的促进作用的研究成果基础之上，以Nuocyte细胞在气道变应性炎症环境下可以诱导T细胞分化并可以放大Th2细胞效应为设想，拟研究Orai1通道干预对小鼠上、下气道变应性炎症环境下该细胞与T、Th2细胞间相互作用的影响。该研究以新近发现的在小鼠对抗寄生虫的II型免疫方面起重要作用的Nuocyte细胞为切入点，研究体内外Nuocyte细胞对初始T细胞分化的诱导作用（包括向Th2或Treg细胞亚类的分化），研究体内外该细胞对Th2细胞功能的促进作用，研究体内外Th2细胞对Nuocyte细胞功能的调控作用，并研究体内外Orai1通道干预对该细胞上述功能的影响。此项目旨在为变应性鼻炎和哮喘的研究开拓新思路，探索新方法，也为开发针对这类疾病的治疗药物提供实验根据和理论基础。