First Author | Chuprin A | Year | 2015 |
Journal | Nat Immunol | Volume | 16 |
Issue | 7 | Pages | 737-45 |
PubMed ID | 26006015 | Mgi Jnum | J:259140 |
Mgi Id | MGI:6142494 | Doi | 10.1038/ni.3194 |
Citation | Chuprin A, et al. (2015) The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nat Immunol 16(7):737-45 |
abstractText | 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. |