AhR signaling reprograms newly activated CD4+ T cells promoting combinatorial expression of regulatory genes to suppress murine GVHD
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ABSTRACT:
PROVIDER: PRJNA325446 | ENA |
REPOSITORIES: ENA
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Project description:AhR activation during the first 3 days of an immune response is sufficient to reprogram CD4+ T cells, resulting in prevention of GVHD. To identify the early transciptional signature of AhR activation in CD4+ T cells, we performed analyses on mice treated with 2 different AhR ligands, TCDD and Cl-BBQ, in comparison with vehicle treated mice. Transcriptional responses were measured by global microarray analysis of donor alloresponding CD4+ T cells from spleen and lymph nodes.
2016-09-01 | GSE83258 | GEO
Project description:AhR activation during the first 3 days of an immune response is sufficient to reprogram CD4+ T cells, resulting in prevention of GVHD. To identify the early transciptional signature of AhR activation in CD4+ T cells, we performed analyses on mice treated with 2 different AhR ligands, TCDD and Cl-BBQ, in comparison with vehicle treated mice. Transcriptional responses were measured by global microarray analysis of donor alloresponding CD4+ T cells from spleen and lymph nodes.
2016-09-01 | GSE83257 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-09-01 | GSE83260 | GEO
Project description:AhR signaling reprograms newly activated CD4+ T cells promoting combinatorial expression of regulatory genes to suppress murine GVHD [48 hr]
| PRJNA325451 | ENA
Project description:AhR signaling reprograms newly activated CD4+ T cells promoting combinatorial expression of regulatory genes to suppress murine GVHD [72 hr]
| PRJNA325450 | ENA
Project description:Interleukin 35-producing B-cells (i35-Bregs) suppress autoimmune diseases and IL-35 is immunosuppressive member of IL-12 cytokine family. It is comprised of p35 and Ebi3 subunits which are assumed to be independently secreted proteins that associate in-vivo to form non-covalently linked heterodimeric IL-35. In view of recent reports that p35 and Ebi3 are not secreted as a heterodimer but act as independent anti-inflammatory cytokines, we investigated whether i35-Bregs can suppress GVHD by secreting p35, Ebi3 or heterodimeric IL-35. Surprisingly, i35-Bregs ameliorate and prolong survival of Graft-Versus-Host-Disease (GVHD) via membrane-bound IL-35 and secrete exosomes with membrane-bound IL-35 (i35-exosomes) that upregulate checkpoint inhibitors (PD-1/LAG-3) and induce T-cell exhaustion, thereby rendering allogeneic T-cells less active, with diminished proinflammatory effects. i35-exosomes also propagate infectious tolerance mechanism by binding bystander B-lymphocytes and converting them to IL-35 producers. Adoptive transfer of i35-Bregs or i35-exosomes suppress GVHD through these mechanisms, indicating that i35-Bregs/i35-exosomes combination-immunotherapy maybe effective therapy for GVHD.
2025-02-24 | GSE263242 | GEO
Project description:Background/Objectives: Aryl hydrocarbon receptor (AHR) ligands are known to suppress antibody production. However, it remains unclear whether this suppression translates into altered antibody-mediated Fcγ receptor signaling in human cells. This study aimed to investigate the effects and mechanisms by which AHR ligands regulate antibody production and antibody-triggered responses in human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were isolated from blood obtained from healthy donors. PBMCs were stimulated with pokeweed mitogen (PWM) to induce IgG1 production or Strept-Biotin IgG1/IgG2 to induce antibody triggered signaling. Before any stimulation, cells were pretreated with vehicle (0.01% DMSO) or AHR ligands TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin), ITE (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester), FICZ (6-formylindolo(3,2-b) carbazole), or I3C (indole 3 carbinol). Results: Our data revealed that PWM stimulation significantly increased IL6 and IL1B gene expression and PWM induced IL-6 cytokine secretion, which was significantly suppressed by TCDD, ITE, FICZ, and I3C. However, only TCDD was able to suppress PWM-stimulated IgG1 antibody production. Transcriptomic analysis revealed that I3C upregulated PWM induced canonical AHR signaling genes such as CYP1A1, CYP1B1, AHRR and TIPARP in human PBMC. Notably, I3C downregulated genes TRAPPC9 and C1QTNF3, which play a role in NF-κB-associated inflammatory signaling. It also revealed potential sex differences in I3C-mediated gene modulation associated with B cell function, Ig expression, FcγR signaling, and inflammatory pathways. Lastly, IgG1 and IgG2 immune complex stimulated IL-6 cytokine secretion was significantly suppressed by TCDD, whereas I3C showed modest suppression. Conclusions: These findings demonstrate that AHR activation suppressed antibody production and IgG-mediated immune signaling in human PBMCs.
2026-09-02 | GSE329255 | GEO
Project description:BACKGROUND - IL-6 mediates graft-versus-host disease (GVHD) in experimental allogeneic stem cell transplantation (alloSCT) and is an attractive therapeutic target. METHODS - A registered phase I/II study (ACTRN12612000726853) of IL-6 receptor (IL-6R) neutralizing antibody administration on day -1 to patients receiving full or reduced-intensity conditioning (RIC) and alloSCT from HLA-matched sibling or unrelated donors with standard cyclosporin and methotrexate GVHD prophylaxis. The primary endpoint was incidence of grade II-IV acute GVHD. Outcomes were compared to a non-randomized but contemporaneous group of study patients receiving the same alloSCT in the absence of IL-6R mAb. FINDINGS - Cytokine and pharmacokinetic analysis confirmed transient IL-6 dysregulation in the first month after alloSCT with complete inhibition following IL-6R mAb administration. With median follow up of 497 days, the incidence of grade II-IV GVHD was 12.5% in recipients of IL-6R inhibition (n = 48) versus 41.5% in the (n = 53) control cohort (P = 0.001). Low rates of acute GVHD were noted in patients receiving IL-6R inhibition relative to control patients following both myeloablative (12.5% vs. 46.4%, P = 0.03) and RIC (12.5% vs. 36.0%, P = 0.04). The incidence of severe (grade III/IV) acute GVHD was 4.2% in recipients of IL-6R inhibition versus 20.8% in the control cohort (P = 0.012). Relapse and chronic GVHD were unchanged. Immune reconstitution was preserved in recipients of IL-6R inhibition, but qualitatively modified with suppression of known pathogenic STAT3-dependent pathways. INTERPRETATION - IL-6 is the principal detectable and dysregulated cytokine secreted after alloSCT and its inhibition is a potential new and simple strategy to protect from acute GVHD despite robust immune reconstitution and a sustained graft-versus-leukemia effect. Single colour, Illumina Human HT12v4 Beadarrays.
2014-09-09 | E-GEOD-61201 | biostudies-arrayexpress
Project description:Many mammalian transcripts contain target sites for multiple miRNAs, although it is not clear to what extent miRNAs may coordinately regulate single genes. We have mapped the interactions between down-regulated miRNAs and overexpressed target protein-coding genes in murine and human lymphomas. Myc, one of the hallmark oncogenes in these lymphomas, stands out as the up-regulated gene with the highest number of genetic interactions with down-regulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach identifies MYC and multiple Myc targets as a preferential target of down-regulated miRNAs in human Burkitt lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately down-regulated to enhance critical oncogenes, such as Myc. Some of these Myc-targeting miRNAs are repressed by Myc, suggesting that these tumors are a consequence of the unbalanced activity of Myc versus miRNAs. This SuperSeries is composed of the following subset Series: GSE29491: Combinatorial effects of microRNA to suppress the myc oncogenic pathway (miRNA data) GSE29492: Combinatorial effects of microRNA to suppress the myc oncogenic pathway (mRNA data)
2012-03-29 | E-GEOD-23026 | biostudies-arrayexpress