Elucidation of Natural Killer T cell development in a mice model of rheumatoid arthritis

类风湿性关节炎小鼠模型中自然杀伤 T 细胞发育的阐明

• 批准号: 20K07538
• 负责人: ディエス ディエゴ
• 金额: $ 2.83万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K07538/
• 关键词: Single Cell Genomics; Immunology; Immune repertoire; Systems Biology; Computational Biology; Systems Immunology; Bioinformatics; Systems immunology; Computational biology

We have reanalyzed the single cell transcriptome data and classify NKT cells in the thymus into several populations including CD4+CD8+ double positive progenitor cells, proliferating cells and NKT1, NKT2 and NKT17 cells. Analysis of the inferred lineage suggests NKT subpopulation phenotype already exists in proliferating cells and is determined during the DP->Proliferating step. A group of pro-apoptotic cells have signatures matching the NKT subpopulations and show increased expression of markers of activation suggesting that overactivation marked them for deletion (negative selection). Most of the cells have a canonical receptor with alpha chain made of TRAV11 and TRAJ18 genes. A fraction of the cells have non-canonical receptors. Although this could represent contaminating cells, non-canonical receptors exist also in differentiated NKT cells. Contaminating cells like developing T cells would show as a distinct clusters, based on our experience with other datasets. NKTs harboring a non-canonical TCR could represent type 2 NKTs, which carry a more diverse TCR.

我们重新分析了单细胞转录组数据，并将胸腺中的NKT细胞分为几个群体，包括CD 4 + CD 8+双阳性祖细胞，增殖细胞和NKT 1，NKT 2和NKT 17细胞。推断谱系的分析表明NKT亚群表型已经存在于增殖细胞中，并且在DP->增殖步骤期间确定。一组促凋亡细胞具有与NKT亚群匹配的特征，并显示活化标志物的表达增加，表明过度活化将其标记为缺失（阴性选择）。大多数细胞具有由TRAV 11和TRAJ 18基因组成的α链的典型受体。一部分细胞具有非典型受体。虽然这可能代表污染细胞，但非典型受体也存在于分化的NKT细胞中。根据我们对其他数据集的经验，像发育中的T细胞这样的污染细胞将显示为不同的簇。携带非典型TCR的NKT可能代表携带更多样化TCR的2型NKT。