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Series GSE32224 Query DataSets for GSE32224
Status Public on Apr 29, 2012
Title Comparison of gene expression in Wild type and T cell-specific conditional Trim28 KO in TCR stimulated and un-stimulated naive CD4 positive and T regulatory cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary A microarray study was performed in unstimulated and TCR-stimulated CD4 + T cells and Treg in wild type and conditional Trim28 KO mice to identify genes that are regulated by Trim28. These experiments constitute a portion of the study described below: Paper Abstract: Peripheral T cell activation and differentiation into specialized effectors are regulated by TCR- and cytokine-mediated signals that induce clonal expansion and unique transcriptional factors. These processes may include active chromatin modification by nuclear factors. In search of such molecules, we found Trim28, a component of large nuclear chromatin-regulatory complex is tightly controlled upon TCR stimulation at the level of phosphorylation, and examined global impact of Trim28 loss in especially CD4+ T cells, by generating T cell-specific conditional Trim28 KO mice (CKO). CD4+ T cells from CKO mice showed defective IL-2 production and T cell proliferation associated with defective upregulation of cell-cycle associated proteins. Accordingly, young CKO showed T-lymphopenia. Surprisingly, Trim28 CKO mice eventually accumulated auto-reactive memory-phenotype T cells that produced inflammatory IL-17. CKO mice are also susceptible to induced auto-inflammatory disease with TH-17 dominant immune response. Loss of Trim28 showed aberrant accumulation of TH-17 and FoxP3+ T cells, two key T cells in inflammation vs. tolerance. We found CKO T cells showed a cell-extrinsic promotion of TH-17 and FoxP3+ T cell development by a mechanism involving overproduction of TGF-beta. Our study revealed unexpected roles of Trim28, a global chromatin regulator in both T cell activation and tolerance.
Overall design Trim28 conditional KO mice and age-matched control mice were sacrificed, and neive CD4+ T cells (CD4+CD62+CD25-) and Treg (CD4+CD62+CD25+) were sorted. Stimulation of naive T cells was done with anti-CD3 and anti-CD28 for 13 hours. We collected quadruplicates for each group.
Contributor(s) Chikuma S, Suita N, Okazaki I, Shibayama S, Honjo T
Citation(s) 22544392
Submission date Sep 19, 2011
Last update date Jan 12, 2017
Contact name Tasuku Honjo
Organization name Kyoto University
Department Department of Immunology and Genomic Medicine
Street address Yoshida Konoe-cho, Sakyo-ku
City Kyoto
ZIP/Postal code 606-8501
Country Japan
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (24)
GSM798457 CD positive WT T cell unstimulated rep1
GSM798458 CD positive WT T cell unstimulated rep2
GSM798459 CD positive WT T cell unstimulated rep3
BioProject PRJNA147217

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE32224_RAW.tar 186.1 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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