Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Cell Rep. 2021 Nov 9;37(6):109969. doi: 10.1016/j.celrep.2021.109969.
MicroRNAs (miRNAs) have emerged as critical regulators of cell fate in the CD8+ T cell response to infection. Although there are several examples of miRNAs acting on effector CD8+ T cells after infection, it is unclear whether differential expression of one or more miRNAs in the naive state is consequential in altering their long-term trajectory. To answer this question, we examine the role of miR-29 in neonatal and adult CD8+ T cells, which express different amounts of miR-29 only prior to infection and adopt profoundly different fates after immune challenge. We find that manipulation of miR-29 expression in the naive state is sufficient for age-adjusting the phenotype and function of CD8+ T cells, including their regulatory landscapes and long-term differentiation trajectories after infection. Thus, miR-29 acts as a developmental switch by controlling the balance between a rapid effector response in neonates and the generation of long-lived memory in adults.
MicroRNAs (miRNAs) 已成为感染后 CD8+ T 细胞反应中细胞命运的关键调节因子。尽管有几个 miRNA 作用于感染后效应 CD8+ T 细胞的例子，但在幼稚状态下一个或多个 miRNA 的差异表达是否会改变它们的长期轨迹尚不清楚。为了回答这个问题，我们研究了 miR-29 在新生儿和成人 CD8+ T 细胞中的作用，这些细胞在感染前仅表达不同量的 miR-29，并且在免疫挑战后采用截然不同的命运。我们发现，在幼稚状态下操纵 miR-29 的表达足以调整 CD8+ T 细胞的表型和功能，包括它们的调节景观和感染后的长期分化轨迹。因此，miR-29 通过控制新生儿快速效应反应和成人产生长寿记忆之间的平衡来充当发育开关。
