N6-甲基腺苷（m6A）是最丰富的表观转录组标记之一，对mRNA代谢的几乎所有方面起着基础作用。虽然m6A编写者和读者已被广泛研究，但m6A橡皮擦的作用尚不清楚。在这里，我们研究了m6A橡皮擦之一FTO在自然杀伤（NK）细胞免疫中的作用。我们观察到FTO缺失的NK细胞过度激活。Fto敲除（Fto-/-）小鼠NK细胞在体内能够防止黑色素瘤转移，而FTO缺失的人类NK细胞能够增强体外对白血病的抗肿瘤反应。我们发现，FTO通过增加细胞因子信号抑制蛋白（SOCS）家族基因的mRNA稳定性，负向调节IL-2 / 15驱动的JAK / STAT信号传导。我们的研究结果表明，FTO是NK细胞免疫的重要调节因子，为异基因NK细胞疗法提供了新的免疫治疗策略。 © 2023作者。

N6 -Methyladenosine (m6 A) is the most abundant epitranscriptomic mark and plays a fundamental role in almost every aspect of mRNA metabolism. Although m6 A writers and readers have been widely studied, the roles of m6 A erasers are not well-understood. Here, we investigate the role of FTO, one of the m6 A erasers, in natural killer (NK) cell immunity. We observe that FTO-deficient NK cells are hyperactivated. Fto knockout (Fto-/- ) mouse NK cells prevent melanoma metastasis in vivo, and FTO-deficient human NK cells enhance the antitumor response against leukemia in vitro. We find that FTO negatively regulates IL-2/15-driven JAK/STAT signaling by increasing the mRNA stability of suppressor of cytokine signaling protein (SOCS) family genes. Our results suggest that FTO is an essential modulator of NK cell immunity, providing a new immunotherapeutic strategy for allogeneic NK cell therapies.© 2023 The Authors.