biostudies-literatureYue XNCRR NIH HHSNIAID NIH HHSNCI NIH HHSNIH HHS2011https://www.ebi.ac.uk/biostudies/studies/S-EPMC6494907biostudies-literatureUnknown10(1)TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3^fl/flFoxp3^Cre mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4⁺Foxp3⁺ and CD4⁺Foxp3^- cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3^fl/flFoxp3^WT/Cre heterozygous female mice are unable to rescue the aberrant properties of Tet2/3Nature communicationsLoss of TET2 and TET3 in regulatory T cells unleashes effector function.PMC6494907R35 CA210043R01 AI128589S10 OD016262S10 RR027366AI 12858901Rao ALi XYue XLio CJSamaniego-Castruita DfalseLoss of TET2 and TET3 in regulatory T cells unleashes effector function.TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3^fl/flFoxp3^Cre mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4⁺Foxp3⁺ and CD4⁺Foxp3^- cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3^fl/flFoxp3^WT/Cre heterozygous female mice are unable to rescue the aberrant properties of Tet2/32019-01-01T00:00:00Z2019 May2026-05-07T03:45:30.459Z2019-06-06T23:10:25ZS-EPMC64949073104360910.1038/s41467-019-09541-y