TY - JOUR TI - The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function AU - Li, Shasha AU - Bern, Michael D AU - Miao, Benpeng AU - Fan, Changxu AU - Xing, Xiaoyun AU - Inoue, Takeshi AU - Piersma, Sytse J AU - Wang, Ting AU - Colonna, Marco AU - Kurosaki, Tomohiro AU - Yokoyama, Wayne M A2 - Belz, Gabrielle T A2 - Rath, Satyajit VL - 11 PY - 2022 DA - 2022/10/03 SP - e77294 C1 - eLife 2022;11:e77294 DO - 10.7554/eLife.77294 UR - https://doi.org/10.7554/eLife.77294 AB - 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. KW - NK cells KW - Bach2 KW - development JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -