中文摘要
γδT细胞是优势定位于粘膜区域免疫器官的T细胞亚群,在肠上皮间淋巴细胞中数量上占优势,被认为在维持肠道区域免疫特性,参与肠道粘膜免疫应答中发挥着重要的作用,然而机制至今尚不明确。只有鉴定出γδT细胞识别的配体,才能彻底澄清其在肠道区域免疫及炎症性肠病发生发展中的作用机制。本研究拟基于高通量测序的免疫组库技术,全面系统的分析小鼠区域免疫器官(肠道、肝脏、肺脏)γδT细胞受体互补决定区3(CDR3)的特征,并以肠道为代表,通过诱导肠炎模型,分析肠道γδT细胞CDR3特征在炎症病理情况下的改变。并通过基因敲除小鼠,建立肠道γδT细胞缺失与炎症损伤程度的关系,说明γδT细胞在炎症性肠病中发挥的作用。最后,根据组库分析得到的炎症特异性CDR3探针,利用基于特异性CDR3的筛选策略,筛选γδT细胞所识别的炎症相关的配体,并验证配体的作用,为揭示肠道区域γδT细胞在炎症性肠病中发挥作用的机制奠定基础。
英文摘要
γδT cells are a subset of T cells predominantly localized at mucosal regional immune organs. Among intestinal intraepithelial lymphocytes (IEL), predominant γδT cells are considered as major players in the maintenance of immunological properties in the intestinal region and the gut mucosal immune response. However, the mechanism underlying γδT cell-mediated mucosal immune response in intestinal region remains unclear. It is essential to identify the ligands recognized by these γδT cells for clarifying the mechanisms underlying γδT cells in intestine regional immunity and the pathogenesis of inflammatory bowel disease (IBD). In this study immune repertoire technique based on high-throughput sequencing will be applied to comprehensively analyze the characteristic of γδT cell receptor (TCR) complementarity determining region 3 (CDR3) in mouse regional immune organs (intestinal, liver, lung). We’ll also analyze the characteristics of γδTCR CDR3 under the condition of inflammatory pathogenesis through the induction of enteritis mouse model. The relationship between the deletion of γδT cells and IBD and the roles of γδT cells in the pathogenesis of enteritis will be investigated by using γδT cell mice. Finally, according to the inflammatory specific CDR3 probe identified in γδTCR immune repertoire, we will screen the ligands of γδTCR associated with inflammation and explore the function of these ligands. This study will provide a basis for better understanding the mechanism of intestine regional γδT cells in the pathogenesis of IBD.
