Induction of pathogenic Th17 cells by salt inducible kinase SGK-1 (SGK-1 KO)
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE43956 |
| Title | Induction of pathogenic Th17 cells by salt inducible kinase SGK-1 (SGK-1 KO) |
| Description | 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. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43956 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE66261
Expression and functions of long noncoding RNAs during human T helper cell differentiation
1
GSE75011
Transcriptional profiling of TH2 cells identifies pathogenic features associated with asthma
1
GSE77105
MicroRNAs 24 and 27 suppress allergic inflammation and target a network of regulators of T helper-2 cell-associated cytokine production
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
