XXXX + regulatory T cell development and function require histone/protein deacetylase 3.

@entity2047 @entity19 @entity409 @entity31934 @entity1960 @entity777 @entity3744 @entity636
@entity409 is associated with a variety of inflammatory diseases. Treg populations are defined by expression of the oligomeric transcription factor @entity3744 and inability to produce @entity2047 , a cytokine required for T cell maintenance and survival. @entity3744 activity is regulated post-translationally by histone/protein acetyltransferases and histone/protein deacetylases (HDACs). Here, we determined that @entity31934 mediates both the development and function of the two main Treg subsets, thymus-derived Tregs and induced Tregs (iTregs). We determined that @entity31934 and @entity3744 physically interact and that @entity31934 expression markedly reduces @entity2047 promoter activity. In @entity19 models, conditional deletion of @entity31934 during thymic Treg development restored Treg production of @entity2047 and blocked the suppressive function of Tregs. @entity31934 -deficient @entity19 died from autoimmunity by 4-6 weeks of age; however, injection of WT @entity3744 + Tregs prolonged survival. Adoptive transfer of @entity31934 -deficient Tregs, unlike WT Tregs, did not control T cell proliferation in naive @entity19 and did not prevent allograft rejection or @entity1960 . @entity31934 also regulated the development of iTregs, as @entity31934 -deficient conventional T cells were not converted into iTregs under polarizing conditions and produced large amounts of @entity2047 , @entity777 , and @entity636 . We conclude that @entity31934 is essential for the normal development and suppressive functions of thymic and peripheral @entity3744 + Tregs.
