The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

Anna Chuprin, Ayelet Avin, Yael Goldfarb, Yonatan Herzig, Ben Levi, Adi Jacob, Asaf Sela, Shir Katz, Moran Grossman, Clotilde Guyon, Moran Rathaus, Haim Y. Cohen, Irit Sagi, Matthieu Giraud, Michael W. McBurney, Eystein S. Husebye, Jakub Abramson

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Aire is a transcriptional regulator that induces the promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for the induction of immunological self-tolerance. Studies have offered molecular insights into how Aire operates, but more comprehensive understanding of this process still remains elusive. Here we found abundant expression of the protein deacetylase Sirtuin-1 (Sirt1) in mature Aire + mTECs, wherein it was required for the expression of Aire-dependent TRA-encoding genes and the subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and identifies a unique function for Sirt1 in preventing organ-specific autoimmunity.

Original languageEnglish
Pages (from-to)737-745
Number of pages9
JournalNature Immunology
Volume16
Issue number7
DOIs
StatePublished - 20 Jul 2015

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© 2015 Nature America, Inc. All rights reserved.

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