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| 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.
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| 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.
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| 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 |
| E-mail(s) |
honjo@mfour.med.kyoto-u.ac.jp
|
| 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 |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| 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 |
| GSM798460 |
CD positive WT T cell unstimulated rep4 |
| GSM798461 |
CD positive WT T cell TCR-stimulated rep1 |
| GSM798462 |
CD positive WT T cell TCR-stimulated rep2 |
| GSM798463 |
CD positive WT T cell TCR-stimulated rep3 |
| GSM798464 |
CD positive WT T cell TCR-stimulated rep4 |
| GSM798465 |
Trim28CKO unstimulated CD4 positve T cell rep1 |
| GSM798466 |
Trim28CKO unstimulated CD4 positve T cell rep2 |
| GSM798467 |
Trim28CKO unstimulated CD4 positve T cell rep3 |
| GSM798468 |
Trim28CKO unstimulated CD4 positve T cell rep4 |
| GSM798469 |
Trim28CKO TCR-stimulated CD4 positve T cell rep1 |
| GSM798470 |
Trim28CKO TCR-stimulated CD4 positve T cell rep2 |
| GSM798471 |
Trim28CKO TCR-stimulated CD4 positve T cell rep3 |
| GSM798472 |
Trim28CKO TCR-stimulated CD4 positve T cell rep4 |
| GSM798473 |
Treg WT rep1 |
| GSM798474 |
Treg WT rep2 |
| GSM798475 |
Treg WT rep3 |
| GSM798476 |
Treg WT rep4 |
| GSM798477 |
Treg Trim28 conditional KO rep1 |
| GSM798478 |
Treg Trim28 conditional KO rep2 |
| GSM798479 |
Treg Trim28 conditional KO rep3 |
| GSM798480 |
Treg Trim28 conditional KO rep4 |
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| Relations |
| BioProject |
PRJNA147217 |
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