SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells

Cell Rep. 2018 Jan 16;22(3):653-665. doi: 10.1016/j.celrep.2017.12.068.

Abstract

A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protection against autoimmunity and enhances self-tolerance by promoting Treg cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1 results in enhanced Treg cell-suppressive function through preventing Foxo1 out of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1 region. Furthermore, our data suggest that SGK1 also plays a critical role in IL-23R-mediated inhibition of Treg and development of Th17 cells. Therefore, we demonstrate that SGK1 functions as a pivotal node in regulating the reciprocal development of pro-inflammatory Th17 and Foxp3+ Treg cells during autoimmune tissue inflammation.

Keywords: Foxo1; Foxp3; IL-23R; Sgk1; Th17 cells; Treg cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • HEK293 Cells
  • Humans
  • Immediate-Early Proteins
  • Mice
  • Mice, Inbred C57BL
  • Protein-Serine-Threonine Kinases
  • Signal Transduction
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / enzymology*
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / cytology*
  • Th17 Cells / enzymology*
  • Th17 Cells / immunology

Substances

  • Immediate-Early Proteins
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase