TGF-β signaling controls Foxp3 methylation and T reg cell differentiation by modulating Uhrf1 activity.

ABSTRACT: Regulatory T (T reg) cells are required for the maintenance of immune homeostasis. Both TGF-β signaling and epigenetic modifications are important for Foxp3 induction, but how TGF-β signaling participates in the epigenetic regulation of Foxp3 remains largely unknown. Here we showed that T cell-specific ablation of Uhrf1 resulted in T reg-biased differentiation in TCR-stimulated naive T cells in the absence of TGF-β signaling, and these Foxp3⁺ T cells had a suppressive function. Adoptive transfer of Uhrf1 ^-/- naive T cells could significantly suppress colitis due to increased iT reg cell generation. Mechanistically, Uhrf1 was induced upon TCR stimulation and participated in the maintenance of DNA methylation patterns of T reg cell-specific genes during ce

SUBMITTER: Sun X 

PROVIDER: S-EPMC6888975 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature