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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 21, 2012 |
Title |
Histone/Protein Deacetylase-6, -9, and Sirtuin-1 Control Foxp3+ Treg Through Shared and Isotype-Specific Mechanisms |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Targeting histone/protein deacetylase (HDAC)-6, -9, or Sirtuin-1 (Sirt1) augments the suppressive functions of Foxp3+ T regulatory (Treg) cells, but it is unclear if this involves different mechanisms, such that combined inhibition would be beneficial. We compared the suppressive functions of Tregs from wild-type C57BL/6 mice or mice with global (HDAC6-/-, HDAC9-/-, dual HDAC6/9-/-) or conditional deletion (CD4-Cre or Foxp3-Cre and floxed Sirt1; GSE26425) alone, or after treatment with isoform-selective HDAC inhibitors (HDACi). We found the heat shock response was crucial in mediating the effects of HDAC6, but not Sirt1 inhibition. Furthermore, while HDAC6, HDAC9 and Sirt1 all deacetylate Foxp3, each has diverse effects on Foxp3 transcription, and loss of HDAC9 is associated with stabilization of Stat5 acetylation and its transcriptional activity. Targeting different HDAC can increase Treg function by multiple and additive mechanisms, indicating the therapeutic potential for combinations of HDACi in the management of autoimmunity and alloresponses post-transplant.
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Overall design |
RNA from three independent samples of magnetically separated CD4+CD25+ Treg of HDAC9-/- mice, compared to wild type (C57BL/6) control.
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Contributor(s) |
Beier UH, Wang L, Han R, Akimova T, Liu Y, Hancock WW |
Citation(s) |
22715468 |
Submission date |
Feb 27, 2012 |
Last update date |
May 04, 2018 |
Contact name |
Wayne W Hancock |
Organization name |
CHOP/UPenn
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Street address |
916B ARC, 3615 Civic Ctr Blvd
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104-4318 |
Country |
USA |
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Platforms (1) |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (6)
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Relations |
BioProject |
PRJNA151799 |
Supplementary file |
Size |
Download |
File type/resource |
GSE36095_RAW.tar |
11.0 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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