The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function.
The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function.
复制标题
转录因子Bach2负调节鼠天然杀伤细胞的成熟和功能。
DOI：
10.7554/elife.77294
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发表时间：
2022-10-03
期刊：
影响因子：
7.7
通讯作者：
Yokoyama WM
中科院分区：
文献类型：
--
作者：
Li S;Bern MD;Miao B;Fan C;Xing X;Inoue T;Piersma SJ;Wang T;Colonna M;Kurosaki T;Yokoyama WM
BTB domain And CNC Homolog 2 （Bach2）是一种转录抑制因子，积极参与T淋巴细胞和B淋巴细胞的发育，但目前尚不清楚Bach2是否也参与先天免疫细胞如自然杀伤细胞（NK）的发育。在这里，我们跟踪了小鼠NK细胞发育过程中Bach2的表达，发现它在未成熟的CD27+CD11b+细胞中达到峰值，并在进一步成熟后下降。Bach2在NK细胞中表现出器官和组织特异性表达模式。Bach2的表达与转录因子TCF1的表达呈正相关，与NK效应分子编码基因和参与细胞周期的基因负相关。Bach2表达缺失导致相应基因染色质可及性的改变。最后，Bach2缺乏导致终分化NK细胞比例增加，颗粒酶和细胞因子的产生增加。在Bach2缺失的情况下，NK细胞介导的肿瘤转移控制也增强了。因此，Bach2是调控NK末端成熟的关键检查点蛋白。
BTB domain And CNC Homolog 2 (Bach2) is a transcription repressor that actively participates in T and B lymphocyte development, but it is unknown if Bach2 is also involved in the development of innate immune cells, such as natural killer (NK) cells. Here, we followed the expression of Bach2 during murine NK cell development, finding that it peaked in immature CD27+CD11b+ cells and decreased upon further maturation. Bach2 showed an organ and tissue-specific expression pattern in NK cells. Bach2 expression positively correlated with the expression of transcription factor TCF1 and negatively correlated with genes encoding NK effector molecules and those involved in the cell cycle. Lack of Bach2 expression caused changes in chromatin accessibility of corresponding genes. In the end, Bach2 deficiency resulted in increased proportions of terminally differentiated NK cells with increased production of granzymes and cytokines. NK cell-mediated control of tumor metastasis was also augmented in the absence of Bach2. Therefore, Bach2 is a key checkpoint protein regulating NK terminal maturation.