|
| Status |
Public on Apr 21, 2013 |
| Title |
Critical Requirement of the DNA Methyltransferase, Dnmt1, for the Development and Function of Foxp3+ Regulatory T Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
We investigated the role of DNMT1 in immune homeostasis by generating mice lacking DNMT1 in Foxp3+ T-regulatory (Treg) cells. These mice showed decreased peripheral Foxp3+ Tregs, complete loss of Foxp3+ Treg suppressive functions in vitro and in vivo, and died from autoimmunity by 3-4 weeks unless they received perinatal transfer of wild-type Tregs that prolonged their survival. Methylation of CpG-sites in the TSDR region of Foxp3 was unaffected by DNMT1 deletion, but microarray revealed more >500 proinflammatory and other genes were upregulated in DNMT1-/- Tregs. CD4-Cre-mediated DNMT1 deletion showed inability of conventional T cells to convert to Foxp3+ Treg under appropriate polarizing conditions. Hence, DNMT1 is absolutely necessary for maintenance of the gene program required for normal Treg development and function.
|
| |
|
| Overall design |
RNA from three independent samples of magnetically separated CD4+CD25+ Treg of fl-DNMT1/Foxp3cre mice, compared to wild type (C57BL6) control
|
| |
|
| Contributor(s) |
Wang L, Liu Y, Han R, Bhatti TR, Beier UH, Akimova T, Hancock WW |
| Citation(s) |
23444399 |
| Submission date |
Feb 22, 2011 |
| Last update date |
May 04, 2018 |
| Contact name |
Wayne W Hancock |
| Organization name |
CHOP/UPenn
|
| Street address |
916B ARC, 3615 Civic Ctr Blvd
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104-4318 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA137079 |
Less...
More...