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

Marc Beyer, Yasser Thabet, Roman Ulrich Müller, Timothy Sadlon, Sabine Classen, Katharina Lahl, Samik Basu, Xuyu Zhou, Samantha L. Bailey-Bucktrout, Wolfgang Krebs, Eva A. Schönfeld, Jan Böttcher, Tatiana Golovina, Christian T. Mayer, Andrea Hofmann, Daniel Sommer, Svenja Debey-Pascher, Elmar Endl, Andreas Limmer, Keli L. HippenBruce R. Blazar, Robert Balderas, Thomas Quast, Andreas Waha, Günter Mayer, Michael Famulok, Percy A. Knolle, Claudia Wickenhauser, Waldemar Kolanus, Bernhard Schermer, Jeffrey A. Bluestone, Simon C. Barry, Tim Sparwasser, James L. Riley, Joachim L. Schultze

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

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 3ĝ€2 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.

Original languageEnglish (US)
Pages (from-to)898-907
Number of pages10
JournalNature immunology
Volume12
Issue number9
DOIs
StatePublished - Sep 2011

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