Regulation of metabolism is emerging as a central mechanism to control cellular identity and function. Extensive research in the last few years has revealed that the PI3K pathway is at the forefront of establishing metabolic changes required for immune cell growth, proliferation, migration, and differentiation. However, we currently have a limited understanding of how signaling through the PI3K pathway is tightly regulated during immune responses and immune cell development. Although a growing number of miRNAs have been shown to target important metabolic pathways, including the PI3K pathway itself, almost nothing is known regarding metabolic regulation by miRNAs in the context of the immune system. Recently, we revealed that the miR-181 family is a metabolic rheostat in vivo through the nonredundant regulation of PTEN. Over the next few years, additional miRNAs with the capacity to regulate various aspects of metabolism in immune cells are likely to be identified. We propose that these miRNAs will form a network to finely tune cellular metabolic status and that miR-181 will function as the primary metabolic rheostat of this network.
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