The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex

  • Nat Immunol. 2014 May;15(5):457-64. doi: 10.1038/ni.2867.
Emily B Heikamp  1 ,  Chirag H Patel  1 ,  Sam Collins  2 ,  Adam Waickman  1 ,  Min-Hee Oh  2 ,  Im-Hong Sun  1 ,  Peter Illei  3 ,  Archna Sharma  4 ,  Aniko Naray-Fejes-Toth  5 ,  Geza Fejes-Toth  5 ,  Jyoti Misra-Sen  4 ,  Maureen R Horton  2 ,  Jonathan D Powell  1
Affiliations
  • 1. Sidney Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 2. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 4. Immune Cells and Inflammation Section, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
  • 5. Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, USA.
PMID: 24705297 DOI: 10.1038/ni.2867
Abstract

SGK1 is an AGC kinase that regulates the expression of membrane sodium channels in renal tubular cells in a manner dependent on the metabolic checkpoint kinase complex mTORC2. We hypothesized that SGK1 might represent an additional mTORC2-dependent regulator of the differentiation and function of T cells. Here we found that after activation by mTORC2, SGK1 promoted T helper type 2 (TH2) differentiation by negatively regulating degradation of the transcription factor JunB mediated by the E3 Ligase Nedd4-2. Simultaneously, SGK1 repressed the production of interferon-γ (IFN-γ) by controlling expression of the long isoform of the transcription factor TCF-1. Consistent with those findings, mice with selective deletion of SGK1 in T cells were resistant to experimentally induced asthma, generated substantial IFN-γ in response to viral Infection and more readily rejected tumors.