SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells

Cell Reports

Timothy Han¹  Vijay Kuchroo¹  Sheng Xiao¹  Theresa Thalhamer¹  Chuan Wu¹  Zuojia Chen¹  Asaf Madi¹ 

[1] Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA;

关键词: Sgk1;    Foxp3;    Foxo1;    Treg cells;    Th17 cells;    IL-23R;   

DOI  :  10.1016/j.celrep.2017.12.068

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown