Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA419679 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6320798.fastq.gz | Fastqsanger.gz | |||
| SRR6320799.fastq.gz | Fastqsanger.gz |
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Project description:Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 transcription factor JunB is required for Th17 cell development. Junb-deficient CD4+ T cells are able to develop in vitro into various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program. Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORt and ROR and reduced expression of Foxp3, a transcription factor known to antagonize RORt function.
2018-02-15 | GSE98242 | GEO
Project description:The AP-1 transcription factor JunB is crucial for multiple biological processes, such as placental development and bone homeostasis. We recently reported that JunB plays an essential role in development of Th17 cells, and thus Junb-deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4+ T cells under other inflammatory disease conditions is unknown. Here we show that mice lacking JunB in CD4+ T cells (Junbfl/flCd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis, a disease model induced by innate immune cells. While the Th17-associated genes Il17a and Il22 are shown to be protective against DSS-induced colitis, their expression was not impaired in the colon of Junbfl/flCd4-Cre mice. In addition to the defect in Th17 development, the colon of Junbfl/flCd4-Cre mice exhibited reduction in regulatory T (Treg) cells. Junb-deficient CD4+ T cells needed high concentration of IL-2 for differentiating into Treg cells in vitro because of their hyporesponsiveness to IL-2. Mechanistically, JunB directly up-regulated expression of CD25, the α−chain of high affinity IL-2 receptor, thereby increasing a sensitivity to IL-2 under Treg-inducing conditions. We uncover a crucial role for JunB in development of Treg cells and defense against an epithelial cell damage-induced colitis.
2022-03-31 | GSE131292 | GEO
Project description:The AP-1 transcription factor JunB is crucial for multiple biological processes, such as placental development and bone homeostasis. We recently reported that JunB plays an essential role in development of Th17 cells, and thus Junb-deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4+ T cells under other inflammatory disease conditions is unknown. Here we show that mice lacking JunB in CD4+ T cells (Junbfl/flCd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis, a disease model induced by innate immune cells. While the Th17-associated genes Il17a and Il22 are shown to be protective against DSS-induced colitis, their expression was not impaired in the colon of Junbfl/flCd4-Cre mice. In addition to the defect in Th17 development, the colon of Junbfl/flCd4-Cre mice exhibited reduction in regulatory T (Treg) cells. Junb-deficient CD4+ T cells needed high concentration of IL-2 for differentiating into Treg cells in vitro because of their hyporesponsiveness to IL-2. Mechanistically, JunB directly up-regulated expression of CD25, the α−chain of high affinity IL-2 receptor, thereby increasing a sensitivity to IL-2 under Treg-inducing conditions. We uncover a crucial role for JunB in development of Treg cells and defense against an epithelial cell damage-induced colitis.
2020-03-31 | GSE120814 | GEO
Project description:Here we identify the activator protein-1 (AP-1) factor JunB as an essential regulator of Th17 cell identity. JunB activates the expression of Th17 lineage-specifying genes, and coordinately represses genes controlling Th1 and Treg fate. Through regulatory analysis, we find that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T cell potential.
2017-06-17 | GSE98413 | GEO
Project description:Here we identify the activator protein-1 (AP-1) factor JunB as an essential regulator of Th17 cell identity. JunB activates the expression of Th17 lineage-specifying genes, and coordinately represses genes controlling Th1 and Treg fate. Through regulatory analysis, we find that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T cell potential.
2017-06-17 | GSE98412 | GEO
Project description:Interleukin 17 (IL-17) producing T helper 17 (Th17) cells are critical drivers of pathogenesis in a variety of autoimmune and inflammatory diseases. Strategies to mitigate excessive Th17 response thus remain an attractive target for immunotherapies. Here we report that Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) regulates IL-17 production by Th17 cells in human and mouse. Using CIP2A knock-out (KO) mice and siRNA-mediated CIP2A silencing in human primary CD4+ T cells, we demonstrated that CIP2A silencing results in a significant increase in IL-17 production. Interestingly, CIP2A deficient Th17 cells were characterized by increased strength and duration of STAT3 (Y705) phosphorylation. Genome-wide gene expression profile as well as the p-STAT3 (Y705) interactome of CIP2A deficient Th17 cells identified that CIP2A regulates the strength of the interaction between Acylglycerol kinase (AGK) and STAT3, and thereby, modulates STAT3 phosphorylation as well as expression of IL-17 in Th17 cells. Our results uncover the physiological function of CIP2A in Th17 cells and provides new opportunities for therapeutic intervention in Th17 cell mediated diseases.
2020-05-26 | PXD010612 | Pride
Project description:Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and RORγt and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and RORγt. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine. The genome-wide binding of STAT3 and STAT5 under Th17 conditions was investigated by CHIP-seq.
2011-02-09 | E-GEOD-26552 | biostudies-arrayexpress
Project description:Th17 cells are key players in autoimmune diseases. However, the roles of non-coding RNAs in Th17 cells are largely unknown. Here, we show that deletion of the Dicer gene specifically in Th17 cells protects from experimental autoimmune encephalomyelitis (EAE). Th17 cells highly express the miR-183/96/182 cluster (miR-183C), in response to IL-6/STAT3 signaling. Moreover, miR-183C regulates pathogenic cytokine expression during Th17 development. Furthermore, transcription factor Foxo1 is one of functional targets of miR-183C in Th17 cells: Foxo1 negatively regulates the pathogenicity of Th17 cells and miR-183C represses Foxo1 expression. Collectively, our results demonstrate one of crucial roles for miR-183C cluster in regulation of Th17 cell function in autoimmune diseases.
2016-06-21 | GSE78505 | GEO
Project description:Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and ROR?t and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and ROR?t. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine. The roles of STAT3 and STAT5 in regulation of gene expression under Th17 differentiation was investigated. Affymetrix Mouse Genome 430 2.0 Arrays were used to evaluate global gene expression.
2011-02-09 | E-GEOD-26551 | biostudies-arrayexpress