Wang Jie, Loveless Ian, Adrianto Indra, Liu Tingting, Subedi Kalpana, Wu Xiaojun, Hossain Md Moazzem, Sebzda Eric, Zhou Li, Mi Qing-Sheng
Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, USA.
Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, USA.
Cell Discov. 2022 Aug 2;8(1):75. doi: 10.1038/s41421-022-00432-z.
Invariant natural killer T cell (iNKT) subsets are differentially distributed in various immune organs. However, it remains unclear whether iNKT cells exhibit phenotypical and functional differences in different peripheral organs and how thymic iNKT cells emigrate to peripheral organs. Here, we used single-cell RNA-seq to map iNKT cells from peripheral organs. iNKT1 cells from liver, spleen, and lymph node appear to have distinct phenotypic profiles and functional capabilities. However, iNKT17 transcriptomes were comparable across peripheral organs. In addition, by integrating data with a thymic iNKT cell study, we uncovered a transient population of recent thymic emigrants, a cluster of peripheral iNKT cells with high expression of transcription factor Kruppel-like factor 2 (Klf2). Deletion of Klf2 led to a severe impairment of iNKT differentiation and migration. Our study revealed that iNKT subsets are uniquely distributed in peripheral organs with some inter-local tissue variation, especially for iNKT1 cell, and identified Klf2 as a rheostat for iNKT cell migration and differentiation.
不变自然杀伤T细胞（iNKT）亚群在各种免疫器官中的分布存在差异。然而，尚不清楚iNKT细胞在不同外周器官中是否表现出表型和功能差异，以及胸腺iNKT细胞如何迁移至外周器官。在此，我们利用单细胞RNA测序来描绘外周器官中的iNKT细胞。来自肝脏、脾脏和淋巴结的iNKT1细胞似乎具有不同的表型特征和功能能力。然而，外周器官中的iNKT17转录组具有可比性。此外，通过将数据与一项胸腺iNKT细胞研究相结合，我们发现了一群近期胸腺迁出的短暂性细胞群，即一群转录因子Kruppel样因子2（Klf2）高表达的外周iNKT细胞。Klf2的缺失导致iNKT分化和迁移严重受损。我们的研究表明，iNKT亚群在外周器官中独特分布，存在一些局部组织差异，尤其是iNKT1细胞，并确定Klf2是iNKT细胞迁移和分化的调节器。
