Eomes 转录因子是不变自然杀伤 T 细胞发育和分化所必需的。
Eomes transcription factor is required for the development and differentiation of invariant NKT cells.
机构信息
Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045 Japan.
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045 Japan.
出版信息
Commun Biol. 2019 Apr 29;2:150. doi: 10.1038/s42003-019-0389-3. eCollection 2019.
Eomes regulates the differentiation of CD8 T cells into effector and memory phases. However, its role in invariant (i)NKT cells remains unknown. Here, we show the impact of Eomes on iNKT cells in the thymus and peripheral tissue using conditional knockout (Eomes-cKO) mice. In the thymus, CD1d-tetramerCD24CD44NK1.1CD69stage 0 iNKT cells express higher levels of Eomes than the other iNKT stages. We also found that Eomes regulates NKT1 cell differentiation predominantly. Interestingly, the expression of Eomes in the steady state is low, but can be upregulated after TCR stimulation. We also showed epigenetic changes in the locus after activation. In addition, vaccination of C57BL/6, but not Eomes-cKO mice with iNKT ligand-loaded dendritic cells generated KLRG1iNKT cells in lung, characterized as effector memory phenotype by transcriptome profiling. Thus, Eomes regulates not only the differentiation of NKT1 cells in the thymus, but also their differentiation into memory-like KLRG1iNKT cells in the periphery.
Eomes 调节 CD8 T 细胞向效应器和记忆阶段的分化。然而，其在不变（i）NKT 细胞中的作用尚不清楚。在这里，我们使用条件敲除（Eomes-cKO）小鼠研究了 Eomes 对胸腺和外周组织中 iNKT 细胞的影响。在胸腺中，CD1d-四聚体+CD24+CD44+NK1.1+CD69+阶段 0 iNKT 细胞比其他 iNKT 阶段表达更高水平的 Eomes。我们还发现 Eomes 主要调节 NKT1 细胞分化。有趣的是，Eomes 在稳态下的表达水平较低，但在 TCR 刺激后可以上调。我们还显示激活后 基因座的表观遗传变化。此外，用负载 iNKT 配体的树突状细胞对 C57BL/6 而非 Eomes-cKO 小鼠进行疫苗接种，可在肺部产生 KLRG1+iNKT 细胞，其转录组谱特征为效应记忆表型。因此，Eomes 不仅调节胸腺中 NKT1 细胞的分化，而且调节它们在外周分化为记忆样 KLRG1+iNKT 细胞。
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