miR-150 通过 c-Myb 调控记忆性 CD8+T 细胞分化。
miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb.
机构信息
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Cell Rep. 2017 Sep 12;20(11):2584-2597. doi: 10.1016/j.celrep.2017.08.060.
MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified. Without miR-150, c-Myb was upregulated and anti-apoptotic targets of c-Myb, such as Bcl-2 and Bcl-xL, were also increased, suggesting a miR-150-c-Myb survival circuit during memory CD8 T cell development. Indeed, overexpression of non-repressible c-Myb rescued the memory CD8 T cell defects caused by overexpression of miR-150. Overall, these results identify a key role for miR-150 in memory CD8 T cells through a c-Myb-controlled enhanced survival circuit.
MicroRNAs 在 T 细胞反应中发挥重要作用。然而，microRNAs 如何调节 CD8 T 细胞记忆仍未得到明确界定。在这里，我们发现 miR-150 在体内负调控 CD8 T 细胞记忆。急性病毒感染后，miR-150 缺失会破坏记忆前体细胞和终末效应 CD8 T 细胞之间的平衡。此外，miR-150 缺陷的记忆性 CD8 T 细胞在再次受到挑战时具有更好的保护作用。确定了 miR-150 通过转录因子 c-Myb 抑制记忆性 CD8 T 细胞发育的关键回路。没有 miR-150，c-Myb 上调，c-Myb 的抗凋亡靶标，如 Bcl-2 和 Bcl-xL，也增加，表明在记忆性 CD8 T 细胞发育过程中存在 miR-150-c-Myb 生存回路。事实上，过表达非抑制性 c-Myb 可挽救由 miR-150 过表达引起的记忆性 CD8 T 细胞缺陷。总体而言，这些结果表明 miR-150 通过 c-Myb 控制的增强生存回路在记忆性 CD8 T 细胞中发挥关键作用。
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