Dataset Information


Induction of pathogenic Th17 cells by salt inducible kinase SGK-1 (NaCl)

ABSTRACT: Th17 cells are highly proinflammatory cells that are critical for clearing extracellular pathogens like fungal infections and for induction of multiple autoimmune diseases1. IL-23 plays a critical role in stabilizing and endowing Th17 cells with pathogenic effector functions2. Previous studies have shown that IL-23 signaling reinforces the Th17 phenotype by increasing expression of IL-23 receptor (IL-23R)3. However, the precise molecular mechanism by which IL-23 sustains the Th17 response and induces pathogenic effector functions has not been elucidated. Here, we used unbiased transcriptional profiling of developing Th17 cells to construct a model of their signaling network and identify major nodes that regulate Th17 development. We identified serum glucocorticoid kinase-1 (SGK1), as an essential node downstream of IL-23 signaling, critical for regulating IL-23R expression and for stabilizing the Th17 cell phenotype by deactivation of Foxo1, a direct repressor of IL-23R expression. A serine-threonine kinase homologous to AKT4, SGK1 has been associated with cell cycle and apoptosis, and has been shown to govern Na+ transport and homeostasis5, 6 7, 8. We here show that a modest increase in salt (NaCl) concentration induces SGK1 expression, promotes IL-23R expression and enhances Th17 cell differentiation in vitro and in vivo, ultimately accelerating the development of autoimmunity. The loss of SGK1 resulted in abrogation of Na+-mediated Th17 differentiation in an IL-23-dependent manner. These data indicate that SGK1 is a critical regulator for the induction of pathogenic Th17 cells and provides a molecular insight by which an environmental factor such as a high salt diet could trigger Th17 development and promote tissue inflammation. Effects of NaCl on Th17 differentiation

ORGANISM(S): Mus musculus  

SUBMITTER: Nir Yosef   Chuan Wu  Vijay K Kuchroo 

PROVIDER: E-GEOD-43957 | ArrayExpress | 2013-03-07



Dataset's files

Action DRS
E-GEOD-43957.idf.txt Idf Processed Raw
E-GEOD-43957.sdrf.txt Txt
Items per page:
1 - 4 of 4

Similar Datasets

2013-03-07 | E-GEOD-43956 | ArrayExpress
2013-01-01 | S-EPMC3637879 | BioStudies
2012-09-01 | E-GEOD-39820 | ArrayExpress
2010-08-31 | E-GEOD-23505 | ArrayExpress
2013-01-01 | S-EPMC3746493 | BioStudies
2010-08-31 | E-GEOD-23681 | ArrayExpress
2009-03-03 | E-GEOD-15029 | ArrayExpress
2018-01-01 | S-EPMC6262360 | BioStudies
2018-01-01 | S-EPMC5826610 | BioStudies
2013-12-03 | E-GEOD-40623 | ArrayExpress