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

Regulatory T cells (T-reg cells) are essential for self-tolerance and immune homeostasis. Lack of effector T cell (T-eff cell) function and gain of suppressive activity by T-reg cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T-reg cells. Foxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 39 untranslated region. Release of SATB1 from the control of Foxp3 in T-reg cells caused loss of suppressive function, establishment of transcriptional T-eff cell programs and induction of T-eff cell cytokines. Our data support the proposal that inhibition of SATB1-mediated modulation of global chromatin remodeling is pivotal for maintaining T-reg cell functionality.