Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2013 May 23;38(5):984-97. doi: 10.1016/j.immuni.2013.02.021. Epub 2013 Apr 25.
Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficient mice showed a complete absence of mature NKT cells in the thymus and periphery. Mechanistically, miR-181 modulated expression of the phosphatase PTEN to control PI3K signaling, which was a primary stimulus for anabolic metabolism in immune cells. Thus miR-181-deficient mice also showed severe defects in lymphoid development and T cell homeostasis associated with impaired PI3K signaling. These results uncover miR-181 as essential for NKT cell development and establish this family of miRNAs as central regulators of PI3K signaling and global metabolic fitness during development and homeostasis.
免疫系统中代谢途径的调节提供了一种主动控制细胞功能、生长、增殖和存活的机制。在这里，我们报告 miR-181 是细胞代谢的非冗余决定因素，对于支持早期 NKT 细胞发育的生物合成需求是必不可少的。结果，miR-181 缺陷型小鼠在胸腺和外周血中完全缺乏成熟的 NKT 细胞。从机制上讲，miR-181 调节磷酸酶 PTEN 的表达以控制 PI3K 信号，PI3K 信号是免疫细胞合成代谢的主要刺激物。因此，miR-181 缺陷型小鼠的淋巴发育和 T 细胞稳态也表现出严重缺陷，与 PI3K 信号受损有关。这些结果揭示了 miR-181 对 NKT 细胞发育的重要性，并确立了这一类 miRNA 作为发育和稳态过程中 PI3K 信号和整体代谢适应性的核心调节剂。
