中文摘要
局部IgE的产生可能是嗜酸粒细胞性鼻息肉发生和发展的关键一环,但其产生的调控机制并不明确。我们前期研究发现鼻息肉中存在异位淋巴组织,这可能是嗜酸粒细胞性鼻息肉局部IgE产生的结构基础;但异位淋巴组织在鼻息肉区域性免疫反应中的基本功能及其形成机制迄今完全不清楚。本课题在前期研究基础上,拟采用分子生物学、流式细胞分析和组织形态学技术,结合细胞培养、小鼠-人鼻息肉组织嵌合体模型和伴异位淋巴组织形成的嗜酸粒细胞性鼻息肉小鼠模型探讨①嗜酸粒细胞性鼻息肉异位淋巴组织的基本功能,包括对初始T和B细胞以及树突状细胞活化和分化的作用;②Th17细胞、B细胞、IL-17、淋巴毒素、自稳性趋化因子在嗜酸粒细胞性鼻息肉异位淋巴组织形成中的作用及机制;力图基本明确异位淋巴组织在鼻息肉区域性免疫反应中的基本功能及其在鼻息肉特定微环境下的形成机制,为最终阐明鼻息肉的发病机制,探寻新的治疗靶点奠定基础。
英文摘要
Previous studies indicate that local IgE production is a critical factor for the development of eosinophilic nasal polyps; however, the regulation of the local IgE production in nasal polyps remains elusive. Our previous research has demonstrated the formation of ectopic lymphoid tissues in nasal polyps, which might be the structure basis for the production of local IgE. The function of ectopic lymphoid structures in nasal polyps and the mechanisms leading to the formation of ectopic lymphoid tissues in nasal polyps are largely unknown. In this project, by means of molecular biology techniques, flow cytometry, histology study, in vitro cell culture, NOD-SCID mice with nasal polyp xenografts, and murine model of eosinophilic nasal polyps with ectopic lymphoid tissue formation, we will try to elucidate: 1) the primary functions of ectopic lymphoid tissues in eosinophilic nasal polyps including supporting the activation and differentiation of T cells, B cells, and dendritic cells; 2) the mechanisms underlying the development of ectopic lymphoid tissues in eosinophilic nasal polyps, including the contribution of Th17 cells, B cells, IL-17, lymphotoxins, and homeostatic chemokines. We believe that this project will provide novel insights into role of ectopic lymphoid tissues in the local immune responses in nasal polyps and the mechanisms leading to the formation of ectopic lymphoid tissues under the specific microenvironment of nasal polyps. This project will also be helpful to finally elucidate the pathogenesis of nasal polyps and to develop novel therapeutic strategies.
