我们和其他学者前期研究显示黏膜组织局部IgE的产生可能是鼻息肉嗜酸粒细胞性炎症的上游诱发因素，靶器官区域性的免疫紊乱可能在疾病发生中起到更重要作用。但鼻息肉组织局部IgE产生的调控机制不明，新近研究显示淋巴器官中的滤泡辅助性T(Tfh)细胞在辅助B细胞产生免疫球蛋白的过程中起关键作用。我们前期研究结果显示鼻息肉组织中存在CXCR5+CD4+ Tfh细胞，但这种淋巴器官以外的Tfh细胞特征如何，是否能够调控鼻黏膜局部IgE的产并不清楚。本课题利用人体鼻息肉组织容易获取的优势，拟通过对比嗜酸和非嗜酸粒细胞性鼻息肉组织Tfh细胞，同时与扁桃体和外周血Tfh细胞比照，采用流式细胞分析技术、体外细胞及组织培养、NOD-SCID小鼠-人鼻息肉组织嵌合体模型等手段探讨Tfh细胞的特征、亚型及其在鼻息肉局部IgE产生中的作用；力图部分揭示鼻黏膜局部IgE产生的调控机制及鼻息肉发病机制。

Our and others published studies have demonstrated that local IgE production may be an upstream event of eosinophilic inflammation in nasal polyps, and local immune disturbance is more important in the pathogenesis of nasal polyps. However, the mechanisms underlying the local IgE production in nasal mucosa remian unclear. T follicular helper (Tfh) cells in lymphoid organs are the specialized CD4+ T cell subset that has evolved appropriate mechanisms to induce the activation and differentiation of B cells into immunoglobulin secreting cells. Our unpublished data have discovered the existence of CXCR5+CD4+ Tfh cells in human nasal polyp tissues; however, the phenotype and the function of these lesional Tfh cells are unknown. In this project, we will take the advantage of the availability of surgical nasal polyp samples and try to elucidate the phenotype and function in local IgE production of mucosal Tfh cells in nasal polyps by means of flow cytometric analysis of human nasal polyp samples, in vitro cell culture and ex vivo tissue culture experiment, and animal experiment using NOD-SCID mice with nasal polyp xenografts. When performing these assays, we will compare the difference between Tfh cells in eosinophilic and non-eosinophilic nasal polyps and the difference between Tfh cells in nasal polyps and those in tonsil and peripheral blood. We believe that this project will provide novel insights into role of nasal mucosal Tfh cells in the local IgE production and the pathogenesis of nasal polyps.