biostudies-literatureBettini MLNIDDK NIH HHSNIAID NIH HHSNCI NIH HHS717-30https://www.ebi.ac.uk/biostudies/studies/S-EPMC3361541biostudies-literatureUnknown36(5)Regulatory T (Treg) cells, driven by the Foxp3 transcription factor, are responsible for limiting autoimmunity and chronic inflammation. We showed that a well-characterized Foxp3(gfp) reporter mouse, which expresses an N-terminal GFP-Foxp3 fusion protein, is a hypomorph that causes profoundly accelerated autoimmune diabetes on a NOD background. Although natural Treg cell development and in vitro function are not markedly altered in Foxp3(gfp) NOD and C57BL/6 mice, Treg cell function in inflammatory environments was perturbed and TGF-β-induced Treg cell development was reduced. Foxp3(gfp) was unable to interact with the histone acetyltransferase Tip60, the histone deacetylase HDAC7, and the Ikaros family zinc finger 4, Eos, which led to reduced Foxp3 acetylation and enhanced K48-linked polyImmunityLoss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency.PMC3361541R01 AI039480DK089125P30 CA021765R01 DK089125R01 CA203689R29 AI039480AI039480CA-21765R01 AI091977AI091977Ziegler SFFinkelstein DBettini MVignali DAPan FBell BDRehg JEBettini MLFloess SPardoll DMHuehn JfalseLoss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency.Regulatory T (Treg) cells, driven by the Foxp3 transcription factor, are responsible for limiting autoimmunity and chronic inflammation. We showed that a well-characterized Foxp3(gfp) reporter mouse, which expresses an N-terminal GFP-Foxp3 fusion protein, is a hypomorph that causes profoundly accelerated autoimmune diabetes on a NOD background. Although natural Treg cell development and in vitro function are not markedly altered in Foxp3(gfp) NOD and C57BL/6 mice, Treg cell function in inflammatory environments was perturbed and TGF-β-induced Treg cell development was reduced. Foxp3(gfp) was unable to interact with the histone acetyltransferase Tip60, the histone deacetylase HDAC7, and the Ikaros family zinc finger 4, Eos, which led to reduced Foxp3 acetylation and enhanced K48-linked poly2012-01-01T00:00:00Z2012 May2025-04-19T17:06:02.094Z2019-03-27T00:53:56ZS-EPMC33615412257947610.1016/j.immuni.2012.03.020