Nature immunology:Natural and inducible T_H17 cells are regulated differently by Akt and mTOR pathways

Natural T helper 17 (nT_H17) 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_H17 cell development. Although Akt and the downstream mTORC1–ARNT–HIFα axis were required for generation of inducible T_H17 (iT_H17) cells, nT_H17 cells developed independently of mTORC1. In contrast, mTORC2 and inhibition of Foxo proteins were critical for development of nT_H17 cells. Moreover, distinct isoforms of Akt controlled the generation of T_H17 cell subsets, as deletion of Akt2, but not of Akt1, led to defective generation of iT_H17 cells. These findings define mechanisms regulating nT_H17 cell development and reveal previously unknown roles of Akt and mTOR in shaping subsets of T cells.

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