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

Jiyeon S. Kim, Tammarah Sklarz, Lauren B. Banks, Mercy Gohil, Adam T. Waickman, Nicolas Skuli, Bryan L. Krock, Chong T. Luo, Weihong Hu, Kristin N. Pollizzi, Ming O. Li, Jeffrey C. Rathmell, Morris J. Birnbaum, Jonathan D. Powell, Martha S. Jordan, Gary A. Koretzky

Research output: Contribution to journalArticlepeer-review

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, nT H17 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 T H17 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.

Original languageEnglish (US)
Pages (from-to)611-618
Number of pages8
JournalNature Immunology
Volume14
Issue number6
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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