Genomewide mapping of Trim33 binding in Th17 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE114119 | GEO | 2018/05/08
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:We report that Tripartite motif-containing 33 (Trim33), a protein that was previously associated with TGF-beta signaling, determines the pathogenic function of Th17 cells. Trim33 deficiency in T cells resulted in resistance to an autoimmune disease model. Lack of Trim33 did not impact TGF-beta signaling in mediating Foxp3 gene expression but greatly reduced TGF-beta induction of IL-17 production during Th17 cell differentiation. Importantly, we found TGF-beta not only increased IL-17 but also suppressed IL-10 expression; absence of Trim33 or Smad2 but not Smad4 in T cells enhanced IL-10 expression. In a Smad2-dependent manner, Trim33 was recruited to Il17 and Il10 gene loci and was crucial in appropriate histone modification accompanying Th17 differentiation. Our study thus demonstrates that Trim33, a non-canonical branch of TGF-beta signaling, programs the pro-inflammatory function of Th17 differentiation by promoting IL-17 and suppressing IL-10 expression. As a critical switch of pathogenic versus regulatory phenotype of T cells, Trim33 may be targeted in treating human autoimmune diseases.
2018-05-02 | GSE113925 | GEO
Project description:Genomewide mapping of Trim33 binding in Th17 cells
| PRJNA464365 | ENA
Project description:Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the interleukin-4 receptor alpha chain (IL-4Rα-R576) biases induced Treg (iTreg) cells towards a T helper 17 (TH17) cell fate. This skewing reflects the recruitment by IL-4Rα-R576 of the adaptor protein growth factor receptor-bound protein 2 (GRB2), which drives IL-17 expression by an extracellular signal-regulated kinase-, IL-6- and STAT3-dependent mechanism. We showed that the IL-4Rα-R576 mutation elicits TH17 airway responses in vivo, in a house dust mite (HDM)- or ovalbumin (OVA)-driven model of airway inflammation in the mice carry the IL-4Rα-R576 mutation (Il4raR576 mice). Treg cell-specific deletion of genes encoding IL-6Rα or the master TH17 cell regulator Retinoid-related Orphan Receptor γt (RORγt), but not IL-4 and IL-13, protected mice against exacerbated airway inflammation induced by IL-4Rα--576. Analysis of lung tissue Treg cells revealed that the expression of IL-17 and the TH17 cell-associated chemokine receptor CCR6 was largely overlapping and highly enriched in Treg and conventional T (Tconv) cells of allergen-treated Il4raR576 mice. To further characterize the subset of IL-17 producing Foxp3+ Treg in the lung of OVA-treated mice we utilized CCR6 as a marker of Treg cells committed towards the TH17 cell lineage to examine their functional, epigenetic and transcriptional profiles. CCR6+Foxp3EGFP+ Treg cells isolated from OVA-sensitized and challenged Il4raR576 mice, by FACS (Fluorescence Activated Cell Sorting) exhibited decreased methylation of the Foxp3 CNS2 locus comparing to CCR6âFoxp3EGFP+ Treg cells from same animals, indicative of decreased stability. They also exhibited profoundly decreased suppressive function as compared to CCR6â WT and CCR6â Il4raR576 counterparts. Transcriptional profiling of CCR6+Foxp3EGFP+ Treg cells revealed increased relative expression in CCR6+ Il4raR576 Treg cells of genes associated with a TH17 cell signature, including Rorc, Ccr6, Il23r, Il17a, Il17f, Il1r1, Nr1d1, Cstl, and Ahr comparing to CCR6âFoxp3EGFP+ Treg cells from same animals. Three CCR6+Foxp3EGFP+ Il4raR576 replicates and four CCR6âFoxp3EGFP+ Il4raR576 Treg replicates (controls) were sampled
2016-07-25 | E-GEOD-80804 | biostudies-arrayexpress
Project description:We previously reported that CCR4+CCR6+Th17 cells are permissive to HIV, while CXCR3+CCR6- Th1 cells are relatively resistant. To identify molecular mechanisms underlying these differences, we performed a genome-wide transcriptional profiling in CXCR3+CCR6-Th1, CCR4+CCR6-Th2, CCR4+CCR6+Th17, and CXCR3+CCR6+Th1Th17 upon TCR triggering. Transcriptional differences between Th17 and Th1 were the most remarkable. HIV-DNA integration was highly efficient in Th17 versus Th1 upon exposure to both wild-type and VSV-G-pseudotyped HIV, indicative that post-entry mechanisms contribute to HIV permissiveness. 4 cell populations from up to 5 donors for a total of 19 samples.
2015-08-30 | E-GEOD-70396 | biostudies-arrayexpress
Project description:Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the interleukin-4 receptor alpha chain (IL-4Rα-R576) biases induced Treg (iTreg) cells towards a T helper 17 (TH17) cell fate. This skewing reflects the recruitment by IL-4Rα-R576 of the adaptor protein growth factor receptor-bound protein 2 (GRB2), which drives IL-17 expression by an extracellular signal-regulated kinase-, IL-6- and STAT3-dependent mechanism. We showed that the IL-4Rα-R576 mutation elicits TH17 airway responses in vivo, in a house dust mite (HDM)- or ovalbumin (OVA)-driven model of airway inflammation in the mice carry the IL-4Rα-R576 mutation (Il4raR576 mice). Treg cell-specific deletion of genes encoding IL-6Rα or the master TH17 cell regulator Retinoid-related Orphan Receptor γt (RORγt), but not IL-4 and IL-13, protected mice against exacerbated airway inflammation induced by IL-4Rα--576. Analysis of lung tissue Treg cells revealed that the expression of IL-17 and the TH17 cell-associated chemokine receptor CCR6 was largely overlapping and highly enriched in Treg and conventional T (Tconv) cells of allergen-treated Il4raR576 mice. To further characterize the subset of IL-17 producing Foxp3+ Treg in the lung of OVA-treated mice we utilized CCR6 as a marker of Treg cells committed towards the TH17 cell lineage to examine their functional, epigenetic and transcriptional profiles. CCR6+Foxp3EGFP+ Treg cells isolated from OVA-sensitized and challenged Il4raR576 mice, by FACS (Fluorescence Activated Cell Sorting) exhibited decreased methylation of the Foxp3 CNS2 locus comparing to CCR6–Foxp3EGFP+ Treg cells from same animals, indicative of decreased stability. They also exhibited profoundly decreased suppressive function as compared to CCR6– WT and CCR6– Il4raR576 counterparts. Transcriptional profiling of CCR6+Foxp3EGFP+ Treg cells revealed increased relative expression in CCR6+ Il4raR576 Treg cells of genes associated with a TH17 cell signature, including Rorc, Ccr6, Il23r, Il17a, Il17f, Il1r1, Nr1d1, Cstl, and Ahr comparing to CCR6–Foxp3EGFP+ Treg cells from same animals.
2016-07-25 | GSE80804 | GEO
Project description:We previously reported that CCR4+CCR6+Th17 cells are permissive to HIV, while CXCR3+CCR6- Th1 cells are relatively resistant. To identify molecular mechanisms underlying these differences, we performed a genome-wide transcriptional profiling in CXCR3+CCR6-Th1, CCR4+CCR6-Th2, CCR4+CCR6+Th17, and CXCR3+CCR6+Th1Th17 upon TCR triggering. Transcriptional differences between Th17 and Th1 were the most remarkable. HIV-DNA integration was highly efficient in Th17 versus Th1 upon exposure to both wild-type and VSV-G-pseudotyped HIV, indicative that post-entry mechanisms contribute to HIV permissiveness.
2015-08-30 | GSE70396 | GEO
Project description:The drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn’s disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patients are rare. We showed that in mLNs, CD could be distinguished from UC by increased frequencies of CCR6+CXCR3-RORg+Tbet-CD4+ (Th17) memory T cells enriched in CD62Llow effector memory T cells (TEM), and their differentially expressed molecular profile. Th17 TEM cells (expressing IL17A, IL17F, RORC and STAT3) displayed a higher pathogenic/cytotoxic (IL23R, IL18RAP, and GZMB, CD160, PRF1) gene signature in CD relative to UC, while non-pathogenic/regulatory genes (IL9, FOXP3, CTLA4) were more elevated in UC. In both CD and UC, IL12 but not IL23, augmented IFNg expression in Th17 TEM and switched their molecular profile towards an ex-Th17 (Th1*)-biased transcriptomic signature (increased IFNG, and decreased TCF7, IL17A), suggesting that Th17 plasticity occurs in mLNs before their recruitment to inflamed colon. We propose that differences observed between Th17 cell frequencies and their molecular profile in CD and UC might have implications in understanding disease pathogenesis, and thus, therapeutic management of patients with IBD.
2019-05-17 | GSE131359 | GEO
Project description:Tripartite motif-containing 33 (Trim33) determines the pathogenic function of Th17 cells
| PRJNA454473 | ENA
Project description:To get insight into TRIM33 functions, TRIM33 ChIP-seq was carried out in murine macrophage cell line (RAW) and in bone marrow-derived macrophages (BMDM). The results showed that, in addition to its role in hematopoietic differentiation, TRIM33 may modulate PU.1 transcriptional activity during macrophage development and/or activation.To characterize the role of TRIM33 in macrophages, we bred TRIM33fl/fl mice with Lyz-Cre mice where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from LyzCre/Trim33+/+ mice and LyzCre/Trim33flox/flox mice were differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Using ChIP-seq, we provide a link between TRIM33 binding and H3K4me3 spreading on inflammatory genes in macrophages. Chromatin immunoprecipitations of TRIM33 and H3K4Me3 followed by multiparallel sequencing performed in murine bone marrow-derived macrophages (BMDM).
2015-11-23 | E-GEOD-43654 | biostudies-arrayexpress
Project description:We compared the methylated and non-methylated regions in the genome of ex vivo-isolated naive CD4+ T cells, Th1 cells, Th17 cells and regulatory T cells by methyl-CpG binding domain protein sequencing (MBD-seq). Naive T cells and Th1 cells share more methylated regions than naive T cells and Th17 cells or Th1 and Th17 cells. However, analysis of the non-methylated regions revealed the highest similarity between Th1 and Th17 cells. Another aim was the analysis of the Th17 lineage on the basis of the methylome. We searched for regions absent in the methylome of Th17 but present in naive T cells, Th1 cells and regulatory T cells. Here, we identified differential methylation in the loci of Il17a, Chn2, Dpp4 and Dclk1. CD4+ T effector cells were prepared ex vivo, stimulated with PMA/Ionomycin, subjected to a comercially available cytokine secretion kit (IL-17A and IFNg), stained by adding fluorescence-labeled antibodies against CD3, CD4 and CD45RB and sorted by flow cytometry. We sorted naive CD4+ T cells (CD3+CD4+CD45RB_high), Th1 cells (CD3+CD4+CD45RB_low_IFNg+IL17A-), Th17 cells (CD3+CD4+CD45RB_low_IFNg-IL17A+) and regulatory T cells (CD3+CD4+CD25++).
2013-12-31 | E-GEOD-45911 | biostudies-arrayexpress