Systematic name M9625
Brief description Genes down-regulated in CD4 [GeneID=920] T helper cells Th0: control versus NaCl treatment.
Full description or 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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 23467085   Authors: Wu C,Yosef N,Thalhamer T,Zhu C,Xiao S,Kishi Y,Regev A,Kuchroo VK
Exact source GSE43957_2410_200_DN
Related gene sets (show 3 additional gene sets from the source publication)

(show 406 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform or
identifier namespace
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 200 genes
Gene families ? Categorize these 200 genes by gene family
Show members (show 200 source identifiers mapped to 200 genes)
Version history 7.3: Moved to ImmuneSigDB sub-collection.

We need your help: Update on GSEA/MSigDB funding support

Last November we submitted a proposal to NCI's Information Technology for Cancer Research (ITCR) program for the continued funding of GSEA and MSigDB. Unfortunately, our proposal was not funded in this round, but we were encouraged to resubmit for the next one. This funding is critical for our continuing support and enhancement of the GSEA-MSigDB resource.

For our original submission many of you sent us emails of support, an important requirement for these grants. We now ask for your help again. We would greatly appreciate a short email message from you describing how the resource has been of value to your work and any concerns you may have about its continued availability.

Please send us your message of support to on or before Monday June 5, 2023.

Thanks in advance for your help and support.
The GSEA/MSigDB Team.

See MSigDB license terms here. Please note that certain gene sets have special access terms.