NKT细胞亚群分析与功能研究

NKT细胞是一类具有CD1d限制性的特殊T淋巴细胞类群。作为连接固有和适应性免疫的重要成员，NKT细胞在多种免疫相关疾病中起到重要的调控作用，然而它们的亚群分型和功能分群至今尚无定论，造成功能与机制研究上的矛盾和困难。针对这一问题，我们利用单细胞测序技术，对小鼠肝脏NKT细胞进行单细胞转录组学分析。结果显示NKT细胞通过基因富集后主要划分为三个亚群，并且可以用特征性表面标记分子Sca-1和CD62L将三个亚群区分开。进一步的研究发现NKT细胞的三个亚群在器官分布上具有特异性，而CD62L单阳性的NKT细胞具更强的抗肿瘤能力。接下来，本申请项目将继续完善NKT细胞亚群新分群体系、深入研究NKT细胞各亚群的分化成熟机制以及他们在肿瘤发生发展中的作用，为NKT细胞各亚群在疾病诊治中的应用提供理论基础。

NKT cells are defined as a special T cell lineage with CD1d restriction. As an important regulator that bridges the innate and adaptive immunity, NKT cells play an important role in the regulation of many immune-related diseases. However, subgroup classification and functional clustering of NKT cells are still unclear, which leads to many contradictions existing in the functional research of NKT cells. Moreover, the inaccuracy of the functional clustering also causes difficulties in the study of mechanisms. In order to solve this problem, we performed single-cell transcriptomics analysis of mouse liver NKT cells using a single cell sequencing technique and found that mouse liver NKT cells could be divided into three groups after gene enrichment, and the three groups are distinguished at the protein level by the characteristic surface markers Sca-1 and CD62L. In further study we also found that the three groups of NKT cells are specific in organ distribution. Importantly, through cell adoptive transfer assays, we found that CD62L single-positive NKT cells showed the strongest anti-tumor effects in mouse tumor models. In this project, we will further improve the subgroup classification and functional clustering of NKT cells, investigate the development and function of NKT cell subsets, and study their roles in the antitumor function, thus to provide theoretical bases for the application of NKT cell subsets in the diagnosis and treatment of diseases.