Autoregulation of Th1-mediated inflammation by twist1
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ABSTRACT:
PROVIDER: PRJNA106287 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series:; GSE11533: Autoregulation of Th1-mediated inflammation by twist1 1st part; GSE11534: Autoregulation of Th1-mediated inflammation by twist1 2nd part Experiment Overall Design: Refer to individual Series
2008-06-18 | E-GEOD-11556 | biostudies-arrayexpress
Project description:The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor κB (NF-κB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We could show that twist1 is expressed by activated T helper (Th) 1 effector memory cells. Induction of twist1 in Th cells is dependent on NF-κB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 is transient following T-cell receptor engagement, and increases upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression is characteristic of repeatedly restimulated effector memory Th cells and thus of the pathogenic memory Th cells of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohn’s disease or ulcerative colitis express high levels of twist1. Expression of twist1 in Th1 lymphocytes limits the expression of the cytokines interferon-γ, IL-2 and tumor necrosis factor-α, and ameliorates Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis. In order to identify the effect of twist1 expression on the function of Th cells, twist1 was ectopically expressed and the transcriptome was compared to empty-virus infected control cells. In addition, this experiment allows for the identification of genes regulated by the transcription factor twist1.
2008-05-24 | GSE11533 | GEO
Project description:Gene expression profiling of repeatedly activated compared to recently activated Th1 cells to identify genes that play a role in chronic inflammatory disorders and may qualify as diagnostic or therapeutic targets; Upon activation under appropriate costimulatory conditions, naive T helper (Th) cells differentiate into Th2 or Th17 cells, each characterized by the expression of specific effector cytokines. In response to a repeated stimulation with antigen, Th cells develop a stable memory for the expression of those cytokines as well as for other secreted or membrane-associated factors. The stable memory for the expression of proinflammatory effector functions may explain the resistance of Th effector cells to conventional immunosuppressive therapy, and the inability of immunosuppression to cure chronic inflammation. The imprinting of the functional memory is based on epigenetic modifications and expression of distinct transcription factors. In this project, we compare the transcriptomes of once and repeatedly activated murine Th1 cells, to identify genes that induce and maintain the functional memory and control the persistence of pathogenic memory Th1 cells. This in turn might help to discriminate pathogenic versus protective cells in immunopathology and present novel targets for the diagnosis and therapy of chronic inflammatory disease.
2008-05-24 | GSE11534 | GEO
Project description:The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor kappaB (NF-kappaB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We show that twist1 is expressed by activated T helper (Th) 1 effector memory (EM) cells. Induction of twist1 in Th cells depended on NF-kappaB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 was transient after T cell receptor engagement, and increased upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression was characteristic of repeatedly restimulated EM Th cells, and thus of the pathogenic memory Th cells characteristic of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohn's disease or ulcerative colitis expressed high levels of twist1. Expression of twist1 in Th1 lymphocytes limited the expression of the cytokines interferon-gamma, IL-2, and tumor necrosis factor-alpha, and ameliorated Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis.
| S-EPMC2525589 | biostudies-literature
Project description:Gene expression profiling of repeatedly activated compared to recently activated Th1 cells to identify genes that play a role in chronic inflammatory disorders and may qualify as diagnostic or therapeutic targets; ; Upon activation under appropriate costimulatory conditions, naive T helper (Th) cells differentiate into Th2 or Th17 cells, each characterized by the expression of specific effector cytokines. In response to a repeated stimulation with antigen, Th cells develop a stable memory for the expression of those cytokines as well as for other secreted or membrane-associated factors. The stable memory for the expression of proinflammatory effector functions may explain the resistance of Th effector cells to conventional immunosuppressive therapy, and the inability of immunosuppression to cure chronic inflammation. The imprinting of the functional memory is based on epigenetic modifications and expression of distinct transcription factors. In this project, we compare the transcriptomes of once and repeatedly activated murine Th1 cells, to identify genes that induce and maintain the functional memory and control the persistence of pathogenic memory Th1 cells. This in turn might help to discriminate pathogenic versus protective cells in immunopathology and present novel targets for the diagnosis and therapy of chronic inflammatory disease. Experiment Overall Design: Genes differentially expressed in once versus four times stimulated Th1 cells. In vitro polarization of murine naïve DO11.10 T cells towards Th1 direction (5 ng/ml recombinant murine IL-12, 5 μg/ml anti-IL-4 antibody) with antigenic stimulation (ova323-339 and irradiated splenic APCs). The transcriptional profiles of resting one week old Th1 (Th1 1w) cells and resting 4 week old Th1 (Th1 4w) cells were compared using Affymetrix Murine Genome (MG) U74V2A GeneChip arrays. Experiment Overall Design: 10 µg of total RNA from each cell sample was reverse transcribed using T7-(d)T24 primer and SuperScript II reverse transcriptase Experiment Overall Design: cDNA extraction with a PhaseLock gel (Eppendorf), and precipitation with ethanol and ammonium acetate Experiment Overall Design: Biotinylated cRNA was transcribed with the MEGAscript high yield transcription kit (Ambion), fragmented, and the hybridization cocktail was prepared (15 µg fragmented biotin-labeled cRNA spiked with Eukaryotic Hybridization control) Experiment Overall Design: probes were subsequently hybridised with the GeneChip U74Av2 for 16 hrs at 45 oC Experiment Overall Design: after washing the hybridisation signals were visualised by staining with streptavidin-phycoerythrin and amplification with an anti-streptavidin antibody Experiment Overall Design: TH1_1w_C1; TH1_1w_C2; TH1_1w_C3TH1_4w_C1; TH1_4w_C2; TH1_4w_C3 Experiment Overall Design: 1w: 1 week in culture; 4w: 4 weeks in culture; C1-3: Culture or Experiment No.
2008-06-18 | E-GEOD-11534 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2008-05-24 | GSE11556 | GEO
Project description:Autoregulation of Th1-mediated inflammation by twist1 1st part
| PRJNA109133 | ENA
Project description:Autoregulation of Th1-mediated inflammation by twist1 2nd part
| PRJNA109135 | ENA
Project description:The immune system can both promote and suppress cancer. Chronic inflammation and proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are considered tumor-promoting. In contrast, the exact nature of protective antitumor immunity remains obscure. In this study, we have quantified locally secreted cytokines during primary immune responses against myeloma and B-cell lymphoma in mice. Strikingly, successful cancer immunosurveillance mediated by tumor-specific CD4+ T cells was consistently associated with elevated local levels of both proinflammatory (IL-1aplha, IL-1beta, and IL-6) and T helper 1 (Th1)-associated cytokines (interferon-alpha, IL-2, IL-12). Cancer eradication was achieved by a collaboration between tumor-specific Th1 cells and tumor-infiltrating, antigen-presenting macrophages. Th1 cells induced secretion of IL-1? and IL-6 by macrophages. Th1-derived interferon-? was shown to render macrophages directly cytotoxic to cancer cells, and to induce macrophages to secrete the angiostatic chemokines CXCL9/MIG and CXCL10/IP-10. Thus, inflammation, when driven by tumor-specific Th1 cells, may prevent rather than promote cancer. Tumoricidal macrophages were isolated from Idiotype-specific TCR-transgenic SCID mice injected with MOPC315-containing Matrigel. Control macrophages were obtained from TCR-transgenic SCID mice injected with Matrigel containing antigen-loss MOPC315.
2011-03-15 | E-GEOD-26912 | biostudies-arrayexpress