SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells

• Published in: Cell reports (Cambridge) Vol. 22; no. 3; pp. 653 - 665
• Main Authors: Wu, Chuan, Chen, Zuojia, Xiao, Sheng, Thalhamer, Theresa, Madi, Asaf, Han, Timothy, Kuchroo, Vijay
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.01.2018; Elsevier
• Subjects: Animals; Cell Differentiation - physiology; Foxo1; Foxp3; HEK293 Cells; Humans; IL-23R; Immediate-Early Proteins; Mice; Mice, Inbred C57BL; Protein Serine-Threonine Kinases; Sgk1; Signal Transduction; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - enzymology; T-Lymphocytes, Regulatory - immunology; Th17 cells; Th17 Cells - cytology; Th17 Cells - enzymology; Th17 Cells - immunology; Treg cells; Treg cells; IL-23R; Foxp3; Sgk1; Foxo1; Th17 cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.12.068

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. [Display omitted] •SGK1 restrains Treg cell expansion and function•SGK1 represses Foxp3 expression via regulating IL-23R•SGK1 reciprocally regulates development of Th17/Treg balance•SGK1 restrains Foxp3 expression via reduced Foxo1 nuclear exclusion 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.