miR-181a-regulated pathways in T-cell differentiation and aging

Abstract MicroRNAs (miRNAs) are regulatory noncoding RNAs important for many aspects of cellular processes including cell differentiation and proliferation. Functions of numerous miRNAs have been identified in T cells, with miR-181a regulating T cell activation thresholds during thymic T cell development and during activation of peripheral T cells. Intriguingly, miR-181a is implicated in defective antiviral and vaccine responses in older individuals, as its expression declines in naïve T cells with increasing age. Here, we review the pathways that are regulated by miR-181a and that explain the unique role of miR-181a in T cell development, T cell activation and antiviral T cell responses. These studies provide a framework for understanding how a decline in miR-181a expression in T cells could contribute to age-related defects in adaptive immunity. We furthermore review the mechanisms that cause the age-related decline in miR-181a expression and discuss the potential of restoring miR-181a expression or targeting miR-181a-regulated pathways to improve impaired T cell responses in older individuals.