title: 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.
authors: Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Jiyeon S
authors: JS
authors: Kim
authors: Tammarah
authors: T
authors: Sklarz
authors: Lauren B
authors: LB
authors: Banks
authors: Mercy
authors: M
authors: Gohil
authors: Adam T
authors: AT
authors: Waickman
authors: Nicolas
authors: N
authors: Skuli
authors: Bryan L
authors: BL
authors: Krock
authors: Chong T
authors: CT
authors: Luo
authors: Weihong
authors: W
authors: Hu
authors: Kristin N
authors: KN
authors: Pollizzi
authors: Ming O
authors: MO
authors: Li
authors: Jeffrey C
authors: JC
authors: Rathmell
authors: Morris J
authors: MJ
authors: Birnbaum
authors: Jonathan D
authors: JD
authors: Powell
authors: Martha S
authors: MS
authors: Jordan
authors: Gary A
authors: GA
authors: Koretzky
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015151:Immunoblotting; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C497397:Arnt protein, mouse; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020381:Interleukin-17; D046912:Multiprotein Complexes; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; C546843:mTOR protein, mouse; C514862:Akt1 protein, mouse; C494922:Akt2 protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
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