Human Gene Set: GSE27896_HDAC6_KO_VS_WT_TREG_DN


Standard name GSE27896_HDAC6_KO_VS_WT_TREG_DN
Systematic name M8246
Brief description Genes down-regulated in T reg: HDAC6 [GeneID=10013] knockout versus wildtype.
Full description or abstract Foxp3+ T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3+ Tregs express histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression and protein function. Pan-HDAC inhibitors developed for oncology enhance Treg production and suppression but have limited non-oncologic applications given their broad effects. We show, using HDAC6-deficient mice and WT mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully MHC-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein, HSP90. Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 21444725   Authors: de Zoeten EF,Wang L,Butler K,Beier UH,Akimova T,Sai H,Bradner JE,Mazitschek R,Kozikowski AP,Matthias P,Hancock WW
Exact source GSE27896_3342_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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