Natural and inducible TH17 cells are regulated differently by Akt and mTOR pathways

The Akt-mTOR axis influences cell activation, differentiation and metabolism. Jordan and colleagues show that thymic and inducible T H 17 cells exhibit different requirements for mTORC1 and mTORC2 as well as Akt isoforms. Natural T helper 17 (nT H 17) cells are a population of interleukin 17 (IL-17)-producing cells that acquire effector function in the thymus during development. Here we demonstrate that the serine/threonine kinase Akt has a critical role in regulating nT H 17 cell development. Although Akt and the downstream mTORC1–ARNT–HIFα axis were required for generation of inducible T H 17 (iT H 17) cells, nT H 17 cells developed independently of mTORC1. In contrast, mTORC2 and inhibition of Foxo proteins were critical for development of nT H 17 cells. Moreover, distinct isoforms of Akt controlled the generation of T H 17 cell subsets, as deletion of Akt2, but not of Akt1, led to defective generation of iT H 17 cells. These findings define mechanisms regulating nT H 17 cell development and reveal previously unknown roles of Akt and mTOR in shaping subsets of T cells.