Natural and inducible [T.sub.H]17 cells are regulated differently by Akt and mTOR pathways

• Published in: Nature immunology Vol. 14; no. 6; pp. 611 - 619
• Main Authors: Kim, Jiyeon S, Sklarz, Tammarah, Banks, Lauren B, Gohil, Mercy, Waickman, Adam T, Skuli, Nicolas, Krock, Bryan L, Luo, Chong T, Hu, Weihong, Pollizzi, Kristin N, Li, Ming O, Rathmell, Jeffrey C, Birnbaum, Morris J, Powell, Jonathan D, Jordan, Martha S, Koretzky, Gary A
• Format: Journal Article
• Language: English
• Published: Nature Publishing Group 01.06.2013
• Subjects: Autoimmunity; Cellular signal transduction; Genetic aspects; Health aspects; T cells; United States
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.2607

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