Single-cell analysis reveals differences among iNKT cells colonizing peripheral organs and identifies Klf2 as a key gene for iNKT emigration.

Single-cell analysis reveals differences among iNKT cells colonizing peripheral organs and identifies Klf2 as a key gene for iNKT emigration.
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单细胞分析揭示了iNKT细胞定殖外周器官之间的差异,并将Klf2鉴定为iNKT迁移的关键基因。

DOI:
10.1038/s41421-022-00432-z
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发表时间:
2022-08-02
期刊:
影响因子:
33.5
通讯作者:
Mi, Qing-Sheng
Mi, Qing-Sheng
中科院分区:
生物学1区
文献类型:
--
作者:
Wang, Jie;Loveless, Ian;Adrianto, Indra;Liu, Tingting;Subedi, Kalpana;Wu, Xiaojun;Hossain, Md Moazzem;Sebzda, Eric;Zhou, Li;Mi, Qing-Sheng

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不变性自然杀伤T细胞(iNKT)亚群在不同的免疫器官中有不同的分布。然而,目前尚不清楚iNKT细胞是否在不同的外周器官中表现出表型和功能差异,以及胸腺iNKT细胞如何向外周器官迁移。在这里,我们使用单细胞RNA-seq来绘制来自外周器官的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,iNKT17转录组在周围器官之间具有可比性。此外,通过将数据与胸腺iNKT细胞研究相结合,我们发现了近期胸腺迁移的瞬时群体,这是一群高表达转录因子kruppel样因子2 (Klf2)的外周iNKT细胞。Klf2的缺失导致iNKT分化和迁移严重受损。我们的研究发现,iNKT亚群独特地分布于外周器官,并存在一些局部组织间变异,尤其是iNKT1细胞,并发现Klf2是iNKT细胞迁移和分化的变阻器。
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.
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