Dataset Information


Autoregulation of Th1-mediated inflammation by twist1 1st part

ABSTRACT: 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. Overall design: Genes differentially expressed upon ectopic twist1 overexpression. Splenic DO11.10 cells were activated in vitro with the cognate peptide ova327-339 in the presence of 1ng/ml IL-12 and 1ng/ml IL-2. On day 2 cells were infected with control virus, or twist1-encoding virus. On day 5 cells were sorted according to expression of the viral marker gene gfp. Cells were restimulated for four hours with PMA/ionomycin. The transcriptional profiles of duplicates of cultures were compared using Affymetrix Murine Genome (MG) 430A 2.0 GeneChip arrays.

INSTRUMENT(S): [Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Pawel Durek  

PROVIDER: GSE11533 | GEO | 2008-05-24



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