壳聚糖作用于肠道CD11b+DC增强B细胞分泌特异性SIgA的分子机制

项目名称： 壳聚糖作用于肠道CD11b+DC增强B细胞分泌特异性SIgA的分子机制

项目编号： No.31270973

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 徐薇

作者单位： 苏州大学

项目金额： 80万元

中文摘要： 对早期抗感染保护具有关键作用的黏膜B细胞SIgA类别转换的细胞与分子免疫学机制尚未阐明。基于我们前期研究发现的壳聚糖（chitosan）递送的DNA疫苗经滴鼻免疫可显著诱导肠道SIgA且与增强的免疫保护相关的基础上，拟深入研究肠道B细胞进行SIgA类别转换的DC调控机制。推测肠道DC亚群经chitosan固有免疫激活通过分泌BAFF、APRIL等以T细胞不依赖方式直接激活B或通过激活CD4+Th细胞间接促进黏膜下B细胞类别转换（CSR）。拟在chitosan-DNA免疫小鼠预防病毒性心肌炎模型中，动态观测肠道DC亚群（CD103+DC,CD11b+DC,TipDC）、SIgA水平及免疫保护的相关性；体外以B-DC-Th-CK共培养，鉴定壳聚糖促进IgA CSR的肠道DC亚群的表型和特征及作用分子机制，解析壳聚糖选择性增强黏膜SIgA的机制，为新型黏膜疫苗设计奠定思路。

中文关键词： 分泌型IgA；壳聚糖；浆细胞样DC；APRIL；TACI

英文摘要： Whether mucosal SIgA level is correlated with anti-microb immunoprotection and the mechanism underlying the induction of SIgA through mucosal B cell class switch recombination (CSR) remains unclear. Mucosal DC has been postulated to facilitate the IgA CSR of mucosal B cells especially in a T-independently fashion. By using chitosan as mucosal delivery carrier, our previous study demonstrated that intranasal immunization with chitosan formulated DNA vaccine significantly enhanced intestinal SIgA production and contributed to the protection against Coxsackievirus B3. To elucidate the underlying cellular and molecular mechanism of mucosal SIgA production through gut B cell CSR, we focused our research on 3 mucosal DC subsets, CD103+DC, CD11b+DC and TipDC, which are postulated to enhance IgA CSR by B cells through direct cytokine stimulation or indirect CD4+Th cell priming. In this study, using CVB3-induced myocarditis as animal model; the dynamic alteration of intestinal CD103+DC, CD11b+DC and TipDC, SIgA level as long with onset of myocarditis would be first studied. Then in an in vitro B-DC-Th-cytokine coculture model, DC's ability to trigger B cell SIgA CSR in presence of antigen, BAFF & APRIL and Th cells would be carefully evaluated. In vivo transfer of purified DC subsets would be performed to see their int

英文关键词： SIgA；chitosan；pDC；APRIL；TACI