Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1

Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1

2013 April 25; 496(7446): 513–517. doi:10.1038/nature11984 | Chuan Wu, Nir Yosef, Theresa Thalhammer, Chen Zhu, Sheng Xiao, Yasuhiro Kishi, Aviv Regev, Vijay Kuchroo
The study investigates the role of serum glucocorticoid kinase-1 (SGK1) in the induction and stabilization of pathogenic Th17 cells, which are crucial for both clearing extracellular pathogens and inducing autoimmune diseases. IL-23 plays a critical role in maintaining the Th17 phenotype by increasing IL-23 receptor (IL-23R) expression and conferring pathogenic effector functions. The authors used transcriptional profiling to construct a signaling network model of Th17 cells and identified SGK1 as a key node downstream of IL-23 signaling. SGK1 is essential for regulating IL-23R expression and stabilizing the Th17 cell phenotype by deactivating Foxo1, a direct repressor of IL-23R expression. The study also shows that a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression, and enhances Th17 cell differentiation both in vitro and in vivo, accelerating autoimmunity. Loss of SGK1 abrogates Na+-mediated Th17 differentiation in an IL-23-dependent manner. These findings provide molecular insights into how environmental factors, such as a high salt diet, can trigger Th17 development and promote tissue inflammation.The study investigates the role of serum glucocorticoid kinase-1 (SGK1) in the induction and stabilization of pathogenic Th17 cells, which are crucial for both clearing extracellular pathogens and inducing autoimmune diseases. IL-23 plays a critical role in maintaining the Th17 phenotype by increasing IL-23 receptor (IL-23R) expression and conferring pathogenic effector functions. The authors used transcriptional profiling to construct a signaling network model of Th17 cells and identified SGK1 as a key node downstream of IL-23 signaling. SGK1 is essential for regulating IL-23R expression and stabilizing the Th17 cell phenotype by deactivating Foxo1, a direct repressor of IL-23R expression. The study also shows that a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression, and enhances Th17 cell differentiation both in vitro and in vivo, accelerating autoimmunity. Loss of SGK1 abrogates Na+-mediated Th17 differentiation in an IL-23-dependent manner. These findings provide molecular insights into how environmental factors, such as a high salt diet, can trigger Th17 development and promote tissue inflammation.
Reach us at info@study.space
[slides] Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1 | StudySpace