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

Abstract

Natural T helper 17 (nTH17) 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 nTH17 cell development. Although Akt and the downstream mTORC1-ARNT-HIFα axis were required for generation of inducible TH17 (iTH17) cells, nTH17 cells developed independently of mTORC1. In contrast, mTORC2 and inhibition of Foxo proteins were critical for development of nTH17 cells. Moreover, distinct isoforms of Akt controlled the generation of TH17 cell subsets, as deletion of Akt2, but not of Akt1, led to defective generation of iTH17 cells. These findings define mechanisms regulating nTH17 cell development and reveal previously unknown roles of Akt and mTOR in shaping subsets of T cells. PMID: 23644504 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: P30 CA016520 NIAMS NIH HHS, United States Grant ID: 5K01AR52802 NIAID NIH HHS, United States Grant ID: T32 AI007247 NIGMS NIH HHS, United States Grant ID: R37 GM053256 NIDDK NIH HHS, United States Grant ID: R01 DK56886 NIGMS NIH HHS, United States Grant ID: R37GM053256 NIDDK NIH HHS, United States Grant ID: R01 DK056886 NIAMS NIH HHS, United States Grant ID: K01 AR052802 More Less keyboard_arrow_down

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady