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Series GSE36095 Query DataSets for GSE36095
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
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.
 
Overall design RNA from three independent samples of magnetically separated CD4+CD25+ Treg of HDAC9-/- mice, compared to wild type (C57BL/6) control.
 
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
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)
GSM881027 Wild type_1
GSM881028 Wild type_2
GSM881029 Wild type_3
Relations
BioProject PRJNA151799

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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