Homo sapiens
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: MODEL2101150001
PROVIDER: PRJNA117127 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:FOXP3-mediated inhibition of a global gene regulator is required for maintaining Treg cell commitment
| PRJNA117309 | ENA
Project description:Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3’UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function. Gene expression profiling of freshly isolated CD4+ T cells, separated into CD25 negative and positive subpopulations, from three different donors. FOXP3 is stably and constitutively expressed at a high level in CD4+CD25+ regulatory T cells and at a low level in CD4+CD25- cells.
2011-08-13 | E-GEOD-15390 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3’UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function.
2011-08-14 | GSE15390 | GEO
Project description:T-cell receptor (TCR) signaling by MHC class-I and -II induces thymocytes to acquire cytotoxic and helper fates via induction of Runx3 or ThPOK transcription factors, respectively. The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. We show that a genome organizer, Satb1, activates genes for lineage-specifying factors, including ThPOK and Runx3, in post-selection thymocytes. Indeed, Satb1-deficient thymocytes are partially redirected to inappropriate T lineages after MHC selection. Although Satb1 is dispensable for maintaining ThPOK in CD4+ T cells, it is necessary for restraining expression of the Treg factor FoxP3. Collectively, our findings demonstrate that Satb1 shapes the primary T-cell pool by initially directing lineage-specific transcriptional programs and subsequently balancing effector versus regulatory subsets via FoxP3 repression.
2017-01-19 | GSE77000 | GEO
Project description:Regulatory T-cell comittment is ensured by inhibition of the global gene regulator SATB1
| PRJNA117597 | ENA
Project description:Foxp3low inflammatory non-suppressive (INS)-regulatory T cells (Tregs) were discovered recently. Unlike conventional Tregs, they produce proinflammatory-cytokines, exhibit reduced suppressiveness, and promote rather than impair anti-tumor immunity. The role of mitochondria in Foxp3low INS-Treg formation in vivo is unclear. We showed that the Foxp3low INS-Treg equivalents in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3low INS-Tregs with mitochondrial dysfunction. The -ketoglutarate-mTORC1 axis was enhanced in these cells. This promoted proinflammatory-cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased -ketoglutarate-derived 2-hydroxyglutarate downregulated Foxp3 expression by methylating the Foxp3-gene regulatory regions. Furthermore, CRIF1-deficiency-induced Foxp3low INS-Tregs suppressed tumor growth in an IFN- dependent manner. Thus, CRIF1-mediated mitochondrial homeostasis is critical for inducing Foxp3low INS-Tregs that promote anti-tumor immunity.
2024-02-28 | GSE233901 | GEO
Project description:Foxp3low inflammatory non-suppressive (INS)-regulatory T cells (Tregs) were discovered recently. Unlike conventional Tregs, they produce proinflammatory-cytokines, exhibit reduced suppressiveness, and promote rather than impair anti-tumor immunity. The role of mitochondria in Foxp3low INS-Treg formation in vivo is unclear. We showed that the Foxp3low INS-Treg equivalents in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3low INS-Tregs with mitochondrial dysfunction. The -ketoglutarate-mTORC1 axis was enhanced in these cells. This promoted proinflammatory-cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased -ketoglutarate-derived 2-hydroxyglutarate downregulated Foxp3 expression by methylating the Foxp3-gene regulatory regions. Furthermore, CRIF1-deficiency-induced Foxp3low INS-Tregs suppressed tumor growth in an IFN- dependent manner. Thus, CRIF1-mediated mitochondrial homeostasis is critical for inducing Foxp3low INS-Tregs that promote anti-tumor immunity.
2024-02-28 | GSE233902 | GEO
Project description:The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+ CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg transcriptional signature. Computational network inference and experimental testing assessed the contribution of several other transcription factors (TFs). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability. To study the impact of FoxP3 and its candidate cofactors (Eos, Gata1, Helios, Irf4, Lef1, Satb1, Xbp1) on the expression of the Treg transcriptional signature, CD4+ conventional T cells (Tconv) activated with anti-CD3+CD28 beads were retrovirally transduced with cDNAs encoding FOXP3, candidate TFs, or a combination of FOXP3 and candidate TFs. After 3 days in culture, the transduced cells were sorted into Trizol, and RNA was purified, labeled and hybridized to Affymetrix arrays.
2012-08-23 | E-GEOD-40274 | biostudies-arrayexpress
Project description:Chronic infections and cancers induce CD8+ T cell exhaustion, but within this exhausted CD8+ T cell pool, a self-renewing, stem-like subset known as progenitor CD8+ T (TPRO) cells play a crucial role in maintaining long-term immunity. These TPRO cells exhibit stem-like characteristics, including quiescence, multipotency, and self-renewal, which are the cardinal features of memory T cells. However, the mechanisms that preserve their stem-like properties under chronic antigen stimulation remain unclear. In this study, we identified that SATB1 as a shared feature is highly expressed in both TPRO and memory CD8+ T cells. While the role of SATB1 in stem-like CD8+ T cells remains unknown, its function as epigenetic regulator in promoting quiescence in hematopoietic stem cells led us to hypothesize that SATB1 plays a pivotal role in regulating the stemness of TPRO and memory CD8+ T cells. To test this hypothesis, we employed CRISPR-mediated gene editing to delete Satb1 gene specifically in CD8+ T cells. Upon chronic LCMV infection, we found that SATB1-deficient CD8+ T cells failed to maintain TPRO subset with enhanced transition towards terminally differentiated cells. Similarly, the SATB1 deficiency in acute viral infection impaired the formation of memory CD8+ T cells. Mechanistically, our multi-omic assays revealed that SATB1 regulates the chromatin accessibility and transcriptional activities of stemness-associated genes, such asTcf7, Bach2,andMyb. Overall, our results underscore the critical role of SATB1 in maintaining the transcriptional and epigenetic features of stem-like CD8+ T cells, shedding light on the previously unappreciated regulatory mechanisms that sustain the stemness of antigen-specific CD8+ T cells.
2025-07-16 | GSE275974 | GEO
Project description:Chronic infections and cancers induce CD8+ T cell exhaustion, but within this exhausted CD8+ T cell pool, a self-renewing, stem-like subset known as progenitor CD8+ T (TPRO) cells play a crucial role in maintaining long-term immunity. These TPRO cells exhibit stem-like characteristics, including quiescence, multipotency, and self-renewal, which are the cardinal features of memory T cells. However, the mechanisms that preserve their stem-like properties under chronic antigen stimulation remain unclear. In this study, we identified that SATB1 as a shared feature is highly expressed in both TPRO and memory CD8+ T cells. While the role of SATB1 in stem-like CD8+ T cells remains unknown, its function as epigenetic regulator in promoting quiescence in hematopoietic stem cells led us to hypothesize that SATB1 plays a pivotal role in regulating the stemness of TPRO and memory CD8+ T cells. To test this hypothesis, we employed CRISPR-mediated gene editing to delete Satb1 gene specifically in CD8+ T cells. Upon chronic LCMV infection, we found that SATB1-deficient CD8+ T cells failed to maintain TPRO subset with enhanced transition towards terminally differentiated cells. Similarly, the SATB1 deficiency in acute viral infection impaired the formation of memory CD8+ T cells. Mechanistically, our multi-omic assays revealed that SATB1 regulates the chromatin accessibility and transcriptional activities of stemness-associated genes, such asTcf7, Bach2,andMyb. Overall, our results underscore the critical role of SATB1 in maintaining the transcriptional and epigenetic features of stem-like CD8+ T cells, shedding light on the previously unappreciated regulatory mechanisms that sustain the stemness of antigen-specific CD8+ T cells.
2025-07-16 | GSE275969 | GEO