Human Gene Set: GSE36095_WT_VS_HDAC9_KO_TREG_DN

Standard name GSE36095_WT_VS_HDAC9_KO_TREG_DN
Systematic name M8936
Brief description Genes down-regulated in T reg: wildtype versus HDAC9 [GeneID=9734] knockout.
Full description or abstract 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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22715468   Authors: Beier UH,Wang L,Han R,Akimova T,Liu Y,Hancock WW
Exact source GSE36095_2870_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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