Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation

Regulatory T cells are essential for self tolerance and immune homeostasis. Lack of T effector -cell function and gain of suppressive activity by T reg are dependent on the transcriptional program induced by FOXP3. Here we identified the repression of SATB1, a genome organizer regulating chromatin structure and gene expression, as a critical event for T reg phenotype and function. FOXP3 acts as a transcriptional repressor directly at the SATB1 locus and indirectly through induction of microRNAs binding to the 3UTR of SATB1 as well as by maintaining a repressive chromatin state of the SATB1 locus. Release of SATB1 from FOXP3 control in T reg causes loss of suppressive function, establishment of transcriptional T effector programs, and induction of T effector cytokines in vitro and in vivo. These data support that inhibition of SATB1mediated modulation of global chromatin remodelling is pivotal for maintaining T reg functionality.