Abdullah Leena, Hills L Benjamin, Winter Evan B, Huang Yina H
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Department of Pathology and Laboratory Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Immunometabolism. 2021;3(1). doi: 10.20900/immunometab20210007. Epub 2021 Jan 28.
Akt kinases translate various external cues into intracellular signals that control cell survival, proliferation, metabolism and differentiation. This review discusses the requirement for Akt and its targets in determining the fate and function of T cells. We discuss the importance of Akt at various stages of T cell development including β-selection during which Akt fulfills the energy requirements of highly proliferative DN3 cells. Akt also plays an integral role in CD8 T cell biology where its regulation of Foxo transcription factors and mTORC1 metabolic activity controls effector versus memory CD8 T cell differentiation. Finally, Akt promotes the differentiation of naïve CD4 T cells into Th1, Th17 and Tfh cells but inhibits the development of Treg cells. We also highlight how modulating Akt in T cells is a promising avenue for enhancing cell-based cancer immunotherapy.
Akt激酶将各种外部信号转化为细胞内信号，从而控制细胞存活、增殖、代谢和分化。本综述讨论了Akt及其靶点在决定T细胞命运和功能方面的必要性。我们讨论了Akt在T细胞发育各个阶段的重要性，包括β选择阶段，在此期间Akt满足高度增殖的双阴性3（DN3）细胞的能量需求。Akt在CD8 T细胞生物学中也起着不可或缺的作用，其对Foxo转录因子和mTORC1代谢活性的调节控制着效应性与记忆性CD8 T细胞的分化。最后，Akt促进初始CD4 T细胞分化为Th1、Th17和滤泡辅助性T（Tfh）细胞，但抑制调节性T（Treg）细胞的发育。我们还强调了调节T细胞中的Akt是增强基于细胞的癌症免疫疗法的一个有前景的途径。
