Format

Send to

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

SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells.

Author information

1
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Electronic address: chuan.wu@nih.gov.
2
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
3
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Electronic address: vkuchroo@evergrande.hms.harvard.edu.

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

PMID:
29346764
PMCID:
PMC5826610
DOI:
10.1016/j.celrep.2017.12.068
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center