MicroRNA-29 specifies age-related differences in the CD8+ T cell immune response
Kristel Joy Yee Mon, Hongya Zhu, Ciarán W.P. Daly, Luyen Tien Vu, Norah L. Smith, Ravi K. Patel, David J. Topham, Kristin Scheible, Kondwani Jambo, Minh T. N. Le, Brian D. Rudd, Andrew Grimson
Abstract
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.