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| Status |
Public on Mar 07, 2013 |
| Title |
Induction of pathogenic Th17 cells by salt inducible kinase SGK-1 (SGK-1 KO) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| |
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| Overall design |
Th17 cells; comparing Sgk1-/- to WT
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| |
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| Contributor(s) |
Wu C, Kuchroo VK |
| Citation(s) |
23467085 |
| Submission date |
Jan 31, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Nir Yosef |
| E-mail(s) |
niryosef@berkeley.edu
|
| Phone |
(617) 714-7734
|
| Organization name |
UC Berkeley
|
| Department |
EECS
|
| Lab |
Yosef
|
| Street address |
Berkeley
|
| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE43970 |
Reconstruction of the dynamic regulatory network that controls Th17 cell differentiation by systematic perturbation in primary cells |
|
| Relations |
| BioProject |
PRJNA188246 |
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