SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells

Chuan Wu, Zuojia Chen, Sheng Xiao, Theresa Thalhamer, Asaf Madi, Timothy Han, Vijay Kuchroo

Research output: Contribution to journalArticlepeer-review

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. Wu et al. demonstrated that SGK1 regulates Treg function in a cell-intrinsic manner. SGK1 functions as a pivotal node in regulating the balance of pro-inflammatory Th17 cells and regulatory Foxp3+ T cells during autoimmune reactions.

Original languageEnglish
Pages (from-to)653-665
Number of pages13
JournalCell Reports
Volume22
Issue number3
DOIs
StatePublished - 16 Jan 2018
Externally publishedYes

Keywords

  • Foxo1
  • Foxp3
  • IL-23R
  • Sgk1
  • Th17 cells
  • Treg cells

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