中文摘要
树突状细胞(dendritic cells,DC)在免疫应答中发挥着重要的正向激发和负向调节作用,其功能调控决定着免疫系统的动态平衡。近年来,申请人围绕DC的功能调控,从免疫微环境、凋亡信号和衰老等因素进行了系统深入研究,提出了原创性的观点,获得了国际同行的认可,文章以共同通讯作者或第一作者发表在Nature Immunology,PNAS, Blood等杂志9篇,单篇最高SCI他引202次,总引用360次。由于DC的抗原交叉递呈功能在病毒和胞内菌感染以及肿瘤的免疫应答中发挥关键作用,而不同的DC亚群,其交叉递呈抗原能力明显不同,申请人将根据已发现的不同DC亚群基因谱表达差异,以Lectin家族作为切入点,对表达差异较大的分子在DC的抗原交叉递呈功能的影响及机制进行系统研究,鉴定影响DC交叉递呈功能的关键分子,以期提高DC在肿瘤治疗中的效果,为DC的临床免疫治疗提供新的靶点和理论依据。
英文摘要
Dendritic cells(DC)play a key role in regulating the dynamic balance of immune system by initiating the immune response and negatively suppressing the immune response. In recent years, the applicant has extensively investigated the regulatory effects of microenvironmental factors, apoptotic signals and aging on DC function. As the co-corresponding author or the first author, I have published 9 research papers in international journals including Nature Immunology, PNAS and Blood with a total citation of 360 , among which one high-impact paper has been cited 202 times. Based on my previous studies, I will continue to work on the cross-presentation of DC since their cross-presentation ability is important for the immune response against virus and intracellular bacterial infections and tumors. My pilot studies on the gene chip analysis of DC subsets with different antigen cross-presentation ability have revealed significant expressional differences in some members of the Lectin family members. Thus, this proposal will aim to determine the role of the moleculars with big expression difference in modulating the cross-presentation of DC and the underlying mechanisms. The expected findings will identify the key factors involved in regulating DC cross-presentation contribute to the development of new strategies for DC immunotherapy.
