Ontology highlight
ABSTRACT:
PROVIDER: PRJNA933282 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Despite their enormous importance, the molecular circuits that control the differentiation of Th17 cells remain largely unknown. Recent studies have reconstructed regulatory networks in mammalian cells, but have focused on short-term responses and relied on perturbation approaches that cannot be applied to primary T cells. Here, we develop a systematic strategy – combining transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based tools for performing gene perturbations in primary T cells – to derive and experimentally validate a temporal model of the dynamic regulatory network that controls Th17 differentiation. The network is arranged into two self-reinforcing and mutually antagonistic modules that either suppress or promote Th17 differentiation. The two modules contain 12 novel regulators with no previous implication in Th17 differentiation, which may be essential to maintain the appropriate balance of Th17 and other CD4+ T cell subsets. Overall, our study identifies and validates 39 regulatory factors that are embedded within a comprehensive temporal network and identifies novel drug targets and organizational principles for the differentiation of Th17 cells. DNA binding of TSC22D3 in Th17 cells compared to WCE
2013-03-07 | E-GEOD-43949 | biostudies-arrayexpress
Project description:The Kaposiâs Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposiâs Sarcoma (KS), which preferentially arise in immunocompromised patients but lack of effective therapeutic options. We have previously shown that KSHV or viral protein LANA can upregulate the glycoprotein CD147 (Emmprin) to induce primary endothelial cell invasiveness, which also requires PI3K/Akt and MAPK activation of VEGF production. In the current study, we first time identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among these downstream genes, ADAMTS1 and 9, two specific metalloproteases are strongly expressed in AIDS-KS tissues and contributed to KSHV-infected cell invasiveness through regulation of related cytokines production and respective receptors expression. By using a nude mice KS-like model, we found that targeting CD147 and downstream ADAMTSs proteins significantly suppressed KSHV-related tumorigenesis in vivo, which is potentially through impairing extracellular matrix (ECM) formation in tumor microenvironment. Taken together, we think that targeting CD147 and related proteins may represent a promising therapeutic strategy against KSHV-related malignancies. HUVEC cells were infected by KSHV or transduced by a CD147 recombinant adenoviral vector and the gene expression signature was compared to respective controls
2016-05-31 | E-GEOD-69067 | biostudies-arrayexpress
Project description:The early stages of human Th17 Cell differentiation were studied using label free proteomics to compare Th17 polarized CD4+ human T cells at 24 h and 72 h with activated cells (72 and 24 h) and Thp cells.
2019-01-28 | PXD008973 | Pride
Project description:Chemokine receptor CCR6 is a G-protein-coupled receptor that binds its high-affinity ligand, CCL20. Among the CD4+ T cells, Th17 and regulatory T cells express CCR6, which facilitates their migration in CCL20-enriched, inflamed tissue. Migration of CCR6+ T cells from secondary lymphoid tissues into inflamed tissues exposes them to a distinct metabolic microenvironment. What drives the metabolic adaptation of cells in these tissues and what contributes to their effector or regulatory function is not clearly understood. During colitis, increased gut production of CCL20 promotes the recruitment of these cells. We demonstrated that the intrinsic signaling of CCL20-CCR6 in CD4+ T cells promotes the differentiation of inflamatory Th1-like Th17 cells (T-bet+RORγt+) during colitis in both mouse models and humans. This signaling induces rapamycin-sensitive phosphorylation of PI3K, Akt, mTORC1, and STAT3 in a CCR6-dependent manner. RNA-seq and proteomics analysis revealed alterations in CCL20 during Th17 differentiation, affecting several metabolic pathways, including energy metabolism. CCL20 significantly increased glycolysis and inhibited oxidative phosphorylation, thereby driving the differentiation of pathogenic Th17 cells. Our findings suggest that alterations in CCR6-induced changes in Th17 metabolism offer an interesting therapeutic target for gut inflammation and autoimmunity.
2025-12-10 | PXD071790 | Pride
Project description:The high mortality caused by severe COVID-19 poses challenges to public health. However, the pathogenesis of severe cases remains a puzzle. Here, we find that SARS-CoV-2 infection boosts CD147 inducible up-regulation, causing persistent virus infection and severe pathological lesions. Specifically, inducible expression of CD147 is transcriptionally regulated by the aryl hydrocarbon receptor (AHR) upon virus infection, while membrane-bound ACE2 decreases, thus indicating that CD147 is a predominant receptor responsible for persistent virus infection. Meanwhile, SARS-CoV-2 infection triggers immune imbalance by promoting cell death of CD4+ T and B cells and abnormal cell communications in rhesus macaque model. Meplazumab, a humanized CD147 antibody, effectively inhibits virus entry and cytokine level, and restores immune balance. We further resolve the cryo-EM structure of CD147-spike complex, and validate five pairs of residues at the interaction interface, which is blocked by Meplazumab via steric hindrance effect. Our findings uncover the pathogenesis of severe COVID-19.
2025-12-02 | GSE298098 | GEO
Project description:The high mortality caused by severe COVID-19 poses challenges to public health. However, the pathogenesis of severe cases remains a puzzle. Here, we find that SARS-CoV-2 infection boosts CD147 inducible up-regulation, causing persistent virus infection and severe pathological lesions. Specifically, inducible expression of CD147 is transcriptionally regulated by the aryl hydrocarbon receptor (AHR) upon virus infection, while membrane-bound ACE2 decreases, thus indicating that CD147 is a predominant receptor responsible for persistent virus infection. Meanwhile, SARS-CoV-2 infection triggers immune imbalance by promoting cell death of CD4+ T and B cells and abnormal cell communications in rhesus macaque model. Meplazumab, a humanized CD147 antibody, effectively inhibits virus entry and cytokine level, and restores immune balance. We further resolve the cryo-EM structure of CD147-spike complex, and validate five pairs of residues at the interaction interface, which is blocked by Meplazumab via steric hindrance effect. Our findings uncover the pathogenesis of severe COVID-19.
2025-12-02 | GSE298097 | GEO
Project description:CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity. Crucial for T helper17 (Th17) cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Examination of Stat3 binding and H3K4me and H3Ac in helper T cells.
2010-08-31 | E-GEOD-23681 | biostudies-arrayexpress
Project description:Determine the role of stat3 phosphorylation, particularly at S727, during the differentiation of Th17 cells.
2025-10-29 | PXD059588 | Pride
Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases.
2025-05-20 | GSE250576 | GEO
Project description:TH17 cells play an important role in host defense especially in barrier organs. Altered functionality of TH17 cells is associated with dysregulated tissue homeostasis resulting in an increased susceptibility for the development of autoimmune diseases. Thus, it is critical to identify mechanisms governing physiological as well as pathophysiological TH17 cell differentiation and identify strategies targeting TH17 cell differentiation in disease settings. Here, we identified the genome organizer Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for TH17 cell development. Satb1 is highly expressed in TH17 cells and loss of Satb1 prevents the differentiation of TH17 cells. As a consequence, expression of Satb1 in CD4+ T cells is required for the formation of TH17 cell-driven autoimmune diseases. Mechanistically, Satb1 mediates TH17 cell development through regulating accessibility of the Il2 gene locus and thereby preventing IL-2 signaling early during TH17 cell differentiation. Thus, Satb1 is critical by suppressing IL-2 expression during the formation of TH17 cells and may be a novel therapeutic target for the treatment of TH17 cell-driven autoimmune diseases
2025-05-20 | GSE290258 | GEO