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

Emily B Heikamp1, Chirag H Patel1, Sam Collins2

  • 1Sidney Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Nature Immunology
|April 8, 2014
PubMed

Insights

Serum- and glucocorticoid-regulated kinase 1 (SGK1) promotes T helper type 2 (TH2) cell differentiation and represses interferon-gamma (IFN-γ) production. SGK1 deficiency in T cells confers resistance to asthma and enhances anti-tumor and anti-viral immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The AGC kinase Serum- and glucocorticoid-regulated kinase 1 (SGK1) is known to regulate sodium channel expression in kidney cells.
  • Its regulation is dependent on the mechanistic target of rapamycin complex 2 (mTORC2).

Purpose of the Study:

  • To investigate the role of SGK1 as a potential regulator of T cell differentiation and function.
  • To explore the link between SGK1, mTORC2, and T cell responses.

Main Methods:

  • Activation of SGK1 by mTORC2.
  • Regulation of JunB degradation by SGK1 and the E3 ligase Nedd4-2.
  • Control of TCF-1 expression by SGK1.
  • Analysis of T cell responses in SGK1-deficient mice.

Main Results:

  • SGK1 promotes T helper type 2 (TH2) differentiation by inhibiting the degradation of the transcription factor JunB.
  • SGK1 represses interferon-gamma (IFN-γ) production by regulating the expression of the long isoform of TCF-1.
  • Mice lacking SGK1 in T cells exhibited resistance to induced asthma, produced more IFN-γ during viral infections, and showed enhanced tumor rejection.

Conclusions:

  • SGK1 is an mTORC2-dependent regulator of T cell differentiation and function.
  • SGK1 plays a critical role in balancing TH2 responses and suppressing IFN-γ production.
  • Targeting SGK1 may offer therapeutic strategies for allergic diseases and cancer.

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